Editing Messenger RNA

{{More citations needed|date=May 2025}}{{short description|RNA that is read by the ribosome to produce a protein}}
{{redirect|MRNA}}
{{distinguish|modRNA}}
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[[Image:MRNA-interaction.svg|thumb|upright=1.2|The "life cycle" of an mRNA in a [[eukaryote|eukaryotic]] cell. [[RNA]] is [[transcription (genetics)|transcribed]] in the [[cell nucleus|nucleus]]; after [[post-transcriptional modification|processing]], it is transported to the [[cytoplasm]] and [[Translation (genetics)|translated]] by the [[ribosome]]. Finally, the mRNA is degraded.]]

In [[molecular biology]], '''messenger ribonucleic acid''' ('''mRNA''') is a single-stranded [[molecule]] of [[RNA]] that corresponds to the [[genetic sequence]] of a [[gene]], and is read by a [[ribosome]] in the process of [[Protein biosynthesis|synthesizing]] a [[protein]].

mRNA is created during the process of [[Transcription (biology)|transcription]], where an [[enzyme]] ([[RNA polymerase]]) converts the gene into [[primary transcript]] mRNA (also known as [[pre-mRNA]]). This pre-mRNA usually still contains [[introns]], regions that will not go on to code for the final [[amino acid sequence]]. These are removed in the process of [[RNA splicing]], leaving only [[exons]], regions that will encode the protein. This exon sequence constitutes [[mature mRNA]]. Mature mRNA is then read by the ribosome, and the ribosome creates the protein utilizing [[amino acids]] carried by [[transfer RNA]] (tRNA). This process is known as [[Translation (biology)|translation]]. All of these processes form part of the [[central dogma of molecular biology]], which describes the flow of genetic information in a biological system.

As in [[DNA]], genetic information in mRNA is contained in the sequence of [[nucleotides]], which are arranged into [[codons]] consisting of three [[ribonucleotide]]s each. Each codon codes for a specific [[amino acid]], except the [[stop codon]]s, which terminate protein synthesis. The translation of codons into amino acids requires two other types of RNA: transfer RNA, which recognizes the codon and provides the corresponding amino acid, and [[ribosomal RNA]] (rRNA), the central component of the ribosome's protein-manufacturing machinery.

The concept of mRNA was developed by [[Sydney Brenner]] and [[Francis Crick]] in 1960 during a conversation with [[François Jacob]]. In 1961, mRNA was identified and described independently by one team consisting of Brenner, Jacob, and [[Matthew Meselson]], and another team led by [[James Watson]]. While analyzing the data in preparation for publication, Jacob and [[Jacques Monod]] coined the name "messenger RNA".
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==Synthesis==
[[File:DNA transcription.svg|thumb|RNA polymerase transcribes a DNA strand to form mRNA]]
The brief existence of an mRNA molecule begins with transcription, and ultimately ends in degradation. During its life, an mRNA molecule may also be processed, edited, and transported prior to translation. Eukaryotic mRNA molecules often require extensive processing and transport, while [[prokaryotes|prokaryotic]] mRNA molecules do not. A molecule of [[Eukaryote|eukaryotic]] mRNA and the proteins surrounding it are together called a [[messenger RNP]].{{cn|date=February 2024}}

===Transcription===
{{main|Transcription (genetics)}}
Transcription is when RNA is copied from DNA in the nucleus. During transcription, [[RNA polymerase]] makes a copy of a gene from the DNA to mRNA as needed. This process differs slightly in eukaryotes and prokaryotes. One notable difference is that prokaryotic RNA polymerase associates with DNA-processing enzymes during transcription so that processing can proceed during transcription. Therefore, this causes the new mRNA strand to become double stranded by producing a complementary strand known as the tRNA strand, which when combined are unable to form structures from base-pairing. Moreover, the template for mRNA is the complementary strand of tRNA, which is identical in sequence to the anticodon sequence that the DNA binds to. The short-lived, unprocessed or partially processed product is termed ''precursor mRNA'', or ''[[pre-mRNA]]''; once completely processed, it is termed ''[[mature mRNA]]''.{{cn|date=February 2024}}

===Uracil substitution for thymine===
mRNA uses uracil (U) instead of thymine (T) in DNA. uracil (U) is the complementary base to adenine (A) during transcription instead of thymine (T). Thus, when using a template strand of DNA to build RNA, thymine is replaced with uracil. This substitution allows the mRNA to carry the appropriate genetic information from DNA to the ribosome for translation. Regarding the natural history, uracil came first then thymine; evidence suggests that RNA came before DNA in evolution.<ref>{{Cite web |title=The Information in DNA Is Decoded by Transcription {{!}} Learn Science at Scitable |url=http://www.nature.com/scitable/topicpage/the-information-in-dna-is-decoded-by-6524808 |access-date=2024-05-03 |website=www.nature.com |language=en}}</ref> The [[RNA World]] hypothesis proposes that life began with RNA molecules, before the emergence of DNA genomes and coded proteins. In DNA, the evolutionary substitution of thymine for uracil may have increased DNA stability and improved the efficiency of DNA replication.<ref>{{Cite web |title=RNA world (article) {{!}} Natural selection |url=https://www.khanacademy.org/science/ap-biology/natural-selection/origins-of-life-on-earth/a/rna-world |access-date=2024-05-03 |website=Khan Academy |language=en}}</ref><ref>{{Cite web |title=The presence of thymine the place of uracil also confers additional stability to DNA. How? |url=https://www.toppr.com/ask/question/the-presence-of-thymine-at-the-place-of-uracil-also-confers-additional-stability-to-dna/ |access-date=2024-05-04 |website=Toppr Ask |language=en}}</ref>

=== Eukaryotic pre-mRNA processing ===
{{main|Post-transcriptional modification}}
[[File:Gene structure eukaryote 2 annotated.svg|thumb|DNA gene is transcribed to pre-mRNA, which is then processed to form a mature mRNA, and then lastly translated by a ribosome to a protein]]
Processing of mRNA differs greatly among [[eukaryote]]s, [[bacteria]], and [[archaea]]. Non-eukaryotic mRNA is, in essence, mature upon transcription and requires no processing, except in rare cases.<ref>{{Cite book| vauthors = Watson JD |author-link=James Watson |title=Molecular Biology of the Gene, 7th edition|publisher=Pearson Higher Ed USA|date=February 22, 2013|isbn=9780321851499}}</ref> Eukaryotic pre-mRNA, however, requires several processing steps before its transport to the cytoplasm and its translation by the ribosome.

==== Splicing ====
{{main|RNA splicing}}
The extensive processing of eukaryotic pre-mRNA that leads to the mature mRNA is the [[RNA splicing]], a mechanism by which [[intron]]s or [[outron]]s (non-coding regions) are removed and [[exon]]s (coding regions) are joined.<ref>{{cite journal | url=https://www.nature.com/articles/s41580-022-00545-z | doi=10.1038/s41580-022-00545-z | title=The physiology of alternative splicing | date=2023 | journal=Nature Reviews Molecular Cell Biology | volume=24 | issue=4 | pages=242–254 | pmid=36229538 | vauthors = Marasco LE, Kornblihtt AR }}</ref><ref>{{cite journal | url=https://www.nature.com/articles/s41576-022-00556-8 | doi=10.1038/s41576-022-00556-8 | title=Regulation of pre-mRNA splicing: Roles in physiology and disease, and therapeutic prospects | date=2023 | journal=Nature Reviews Genetics | volume=24 | issue=4 | pages=251–269 | pmid=36526860 | vauthors = Rogalska ME, Vivori C, Valcárcel J }}</ref>

==== 5' cap addition ====
{{main|5' cap}}
[[File:5' cap labeled.svg|thumb|5' cap structure]]
A ''5' cap'' (also termed an RNA cap, an RNA [[7-methylguanosine]] cap, or an RNA m<sup>7</sup>G cap) is a modified guanine nucleotide that has been added to the "front" or [[5' end]] of a eukaryotic messenger RNA shortly after the start of transcription. The 5' cap consists of a terminal 7-methylguanosine residue that is linked through a 5'-5'-triphosphate bond to the first transcribed nucleotide. Its presence is critical for recognition by the [[ribosome]] and protection from [[RNase]]s.{{cn|date=February 2024}}

Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences the other. Shortly after the start of transcription, the 5' end of the mRNA being synthesized is bound by a [[Capping enzyme|cap-synthesizing complex]] associated with [[RNA polymerase]]. This [[enzyme|enzymatic]] complex [[catalyze]]s the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step [[biochemistry|biochemical]] reaction.{{cn|date=February 2024}}

====Editing====
In some instances, an mRNA will be [[RNA editing|edited]], changing the nucleotide composition of that mRNA. An example in humans is the [[apolipoprotein B#RNA editing|apolipoprotein B]] mRNA, which is edited in some tissues, but not others. The editing creates an early stop codon, which, upon translation, produces a shorter protein. Another well-defined example is A-to-I (adenosine to inosine) editing, which is carried out by double-strand specific adenosine-to inosine editing (ADAR) enzymes. This can occur in both the open reading frame and untranslated regions, altering the structural properties of the mRNA. Although essential for development, the exact role of this editing is not fully understood <ref>{{cite journal | doi=10.1186/gm508 | doi-access=free | title=Adenosine-to-inosine RNA editing and human disease | date=2013 | journal=Genome Medicine | volume=5 | issue=11 | page=105 | pmid=24289319 | pmc=3979043 | vauthors = Slotkin W, Nishikura K }}</ref>

==== Polyadenylation ====
{{main|Polyadenylation}}
[[File:Polyadenylation.png|thumb|Polyadenylation]]
Polyadenylation is the covalent linkage of a polyadenylyl moiety to a messenger RNA molecule. In eukaryotic organisms most messenger RNA (mRNA) molecules are polyadenylated at the 3' end, but recent studies have shown that short stretches of uridine (oligouridylation) are also common.<ref name="Choi_2012">{{cite journal | vauthors = Choi YS, Patena W, Leavitt AD, McManus MT | title = Widespread RNA 3'-end oligouridylation in mammals | journal = RNA | volume = 18 | issue = 3 | pages = 394–401 | date = March 2012 | pmid = 22291204 | pmc = 3285928 | doi = 10.1261/rna.029306.111 }}</ref> The [[messenger RNA#Poly(A) tail|poly(A) tail]] and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. mRNA can also be polyadenylated in prokaryotic organisms, where poly(A) tails act to facilitate, rather than impede, exonucleolytic degradation.{{cn|date=February 2024}}

Polyadenylation occurs during and/or immediately after transcription of DNA into RNA. After transcription has been terminated, the mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. After the mRNA has been cleaved, around 250 adenosine residues are added to the free 3' end at the cleavage site. This reaction is catalyzed by [[polyadenylate polymerase]]. Just as in [[alternative splicing]], there can be more than one polyadenylation variant of an mRNA.

Polyadenylation site mutations also occur. The primary RNA transcript of a gene is cleaved at the poly-A addition site, and 100–200 A's are added to the 3' end of the RNA. If this site is altered, an abnormally long and unstable mRNA construct will be formed.

===Transport===
Another difference between eukaryotes and prokaryotes is mRNA transport. Because eukaryotic transcription and translation is compartmentally separated, eukaryotic mRNAs must be exported from the [[cell nucleus|nucleus]] to the [[cytoplasm]]—a process that may be regulated by different signaling pathways.<ref name=Quaresma2013>{{cite journal | vauthors = Quaresma AJ, Sievert R, Nickerson JA | title = Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway | journal = Molecular Biology of the Cell | volume = 24 | issue = 8 | pages = 1208–1221 | date = April 2013 | pmid = 23427269 | pmc = 3623641 | doi = 10.1091/mbc.E12-06-0450 }}</ref> Mature mRNAs are recognized by their processed modifications and then exported through the [[nuclear pore]] by binding to the cap-binding proteins CBP20 and CBP80,<ref name=kierzkowski2009>{{cite journal | vauthors = Kierzkowski D, Kmieciak M, Piontek P, Wojtaszek P, Szweykowska-Kulinska Z, Jarmolowski A | title = The Arabidopsis CBP20 targets the cap-binding complex to the nucleus, and is stabilized by CBP80 | journal = The Plant Journal | volume = 59 | issue = 5 | pages = 814–825 | date = September 2009 | pmid = 19453442 | doi = 10.1111/j.1365-313X.2009.03915.x | doi-access = free }}</ref> as well as the transcription/export complex (TREX).<ref name=strausser2002>{{cite journal | vauthors = Strässer K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondón AG, Aguilera A, Struhl K, Reed R, Hurt E | title = TREX is a conserved complex coupling transcription with messenger RNA export | journal = Nature | volume = 417 | issue = 6886 | pages = 304–308 | date = May 2002 | pmid = 11979277 | doi = 10.1038/nature746 | bibcode = 2002Natur.417..304S | s2cid = 1112194 }}</ref><ref name=katahira2014>{{cite journal | vauthors = Katahira J, Yoneda Y | title = Roles of the TREX complex in nuclear export of mRNA | journal = RNA Biology | volume = 6 | issue = 2 | pages = 149–152 | date = 27 October 2014 | pmid = 19229134 | doi = 10.4161/rna.6.2.8046 | doi-access = free }}</ref> Multiple mRNA export pathways have been identified in eukaryotes.<ref name="Cenik2011">{{cite journal | vauthors = Cenik C, Chua HN, Zhang H, Tarnawsky SP, Akef A, Derti A, Tasan M, Moore MJ, Palazzo AF, Roth FP | title = Genome analysis reveals interplay between 5'UTR introns and nuclear mRNA export for secretory and mitochondrial genes | journal = PLOS Genetics | volume = 7 | issue = 4 | pages = e1001366 | date = April 2011 | pmid = 21533221 | pmc = 3077370 | doi = 10.1371/journal.pgen.1001366 | doi-access = free }}</ref>

In spatially complex cells, some mRNAs are transported to particular subcellular destinations. In mature [[neuron]]s, certain mRNA are transported from the [[Soma (biology)|soma]] to [[dendrite]]s. One site of mRNA translation is at polyribosomes selectively localized beneath synapses.<ref>{{cite journal | vauthors = Steward O, Levy WB | title = Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus | journal = The Journal of Neuroscience | volume = 2 | issue = 3 | pages = 284–291 | date = March 1982 | pmid = 7062109 | pmc = 6564334 | doi = 10.1523/JNEUROSCI.02-03-00284.1982 }}</ref> The mRNA for [[Arc/Arg3.1]] is induced by synaptic activity and localizes selectively near active [[synapse]]s based on signals generated by [[NMDA receptor]]s.<ref>{{cite journal | vauthors = Steward O, Worley PF | title = Selective targeting of newly synthesized Arc mRNA to active synapses requires NMDA receptor activation | journal = Neuron | volume = 30 | issue = 1 | pages = 227–240 | date = April 2001 | pmid = 11343657 | doi = 10.1016/s0896-6273(01)00275-6 | s2cid = 13395819 | doi-access = free }}</ref> Other mRNAs also move into dendrites in response to external stimuli, such as [[β-actin]] mRNA.<ref name=Job1912>{{cite journal | vauthors = Job C, Eberwine J | title = Localization and translation of mRNA in dendrites and axons | journal = Nature Reviews. Neuroscience | volume = 2 | issue = 12 | pages = 889–898 | date = December 2001 | pmid = 11733796 | doi = 10.1038/35104069 | author-link2 = James Eberwine | s2cid = 5275219 }}</ref> For export from the nucleus, actin mRNA associates with [[ZBP1]]<ref name=Oleynikov2003>{{cite journal | vauthors = Oleynikov Y, Singer RH | title = Real-time visualization of ZBP1 association with beta-actin mRNA during transcription and localization  | journal = Current Biology | volume = 13 | issue = 3 | pages = 199–207 | date = February 2003 | pmid =  12573215 | pmc = 4765734 | doi = 10.1016/s0960-9822(03)00044-7 | bibcode = 2003CBio...13..199O }}</ref> and later with [[Eukaryotic small ribosomal subunit (40S)|40S subunit]]. The complex is bound by a [[motor protein]] and is transported to the target location ([[Neurite|neurite extension]]) along the [[cytoskeleton]]. Eventually ZBP1 is [[Phosphorylation|phosphorylated]] by [[Src family kinase|Src]] in order for translation to be initiated.<ref name="Hüttelmaier_2005">{{cite journal | vauthors = Hüttelmaier S, Zenklusen D, Lederer M, Dictenberg J, Lorenz M, Meng X, Bassell GJ, Condeelis J, Singer RH | display-authors = 6 | title = Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1 | journal = Nature | volume = 438 | issue = 7067 | pages = 512–515 | date = November 2005 | pmid = 16306994 | doi = 10.1038/nature04115 | s2cid = 2453397 | bibcode = 2005Natur.438..512H }}</ref> In developing neurons, mRNAs are also transported into growing [[axon]]s and especially growth cones. Many mRNAs are marked with so-called "zip codes", which target their transport to a specific location.<ref name=Oleynikov1998>{{cite journal | vauthors = Oleynikov Y, Singer RH | title = RNA localization: different zipcodes, same postman? | journal = Trends in Cell Biology | volume = 8 | issue = 10 | pages = 381–383 | date = October 1998 | pmid =  9789325 | pmc = 2136761 | doi = 10.1016/s0962-8924(98)01348-8 }}</ref><ref name=Ainger1997>{{cite journal | vauthors = Ainger K, Avossa D, Diana AS, Barry C, Barbarese E, Carson JH | title = Transport and localization elements in myelin basic protein mRNA | journal = The Journal of Cell Biology | volume = 138 | issue = 5 | pages = 1077–1087 | date = September 1997 | pmid = 9281585 | pmc = 2136761 | doi = 10.1083/jcb.138.5.1077 }}</ref> mRNAs can also transfer between mammalian cells through structures called [[tunneling nanotube]]s.<ref>{{cite journal | vauthors = Haimovich G, Ecker CM, Dunagin MC, Eggan E, Raj A, Gerst JE, Singer RH | title = Intercellular mRNA trafficking via membrane nanotube-like extensions in mammalian cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 46 | pages = E9873–E9882 | date = November 2017 | pmid = 29078295 | pmc = 5699038 | doi = 10.1073/pnas.1706365114 | bibcode = 2017PNAS..114E9873H | doi-access = free }}</ref><ref>{{Cite journal | vauthors = Haimovich G, Dasgupta S, Gerst JE  |title=RNA transfer through tunneling nanotubes | journal = Biochemical Society Transactions | date = February 2021| volume = 49 | issue = 1 | pages = 145–160 |url=https://portlandpress.com/biochemsoctrans/article-abstract/49/1/145/227426/RNA-transfer-through-tunneling-nanotubes |doi=10.1042/BST20200113|pmid=33367488 |s2cid=229689880 }}</ref>

===Translation===
{{main|Translation (biology)}}
[[File:Peptide syn.svg|thumb|Translation of mRNA to protein]]
Because prokaryotic mRNA does not need to be processed or transported, translation by the [[ribosome]] can begin immediately after the end of transcription. Therefore, it can be said that prokaryotic translation is ''coupled'' to transcription and occurs ''co-transcriptionally''. <ref>{{cite journal | doi=10.3389/fmicb.2020.624830 | doi-access=free | title=Coupled Transcription-Translation in Prokaryotes: An Old Couple with New Surprises | date=2021 | journal=Frontiers in Microbiology | volume=11 | vauthors = Irastortza-Olaziregi M, Amster-Choder O | pmid=33552035 | pmc=7858274 }}</ref>

Eukaryotic mRNA that has been processed and transported to the cytoplasm (i.e., mature mRNA) can then be translated by the ribosome. Translation may occur at ribosomes free-floating in the cytoplasm, or directed to the [[endoplasmic reticulum]] by the [[signal recognition particle]]. Therefore, unlike in prokaryotes, eukaryotic translation ''is not'' directly coupled to transcription. It is even possible in some contexts that reduced mRNA levels are accompanied by increased protein levels, as has been observed for mRNA/protein levels of [[Eukaryotic translation elongation factor 1 alpha 1|EEF1A1]] in [[breast cancer]].<ref name=Lin2018>{{cite journal | vauthors = Lin CY, Beattie A, Baradaran B, Dray E, Duijf PH | title = Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress | journal = Scientific Reports | volume = 8 | issue = 1 | pages = 13904 | date = September 2018 | pmid = 30224719 | pmc = 6141510 | doi = 10.1038/s41598-018-32272-x | bibcode = 2018NatSR...813904L }}</ref>{{Primary source inline|date=June 2021}}

== Structure ==
[[File:MRNA structure.svg|thumb|700px|center|The structure of a mature eukaryotic mRNA. A fully processed mRNA includes a [[5' cap]], [[5' UTR]], [[coding region]], [[3' UTR]], and poly(A) tail.]]

=== Coding regions ===
{{main|Coding region}}
Coding regions are composed of [[codons]], which are decoded and translated into proteins by the ribosome; in eukaryotes usually into one and in prokaryotes usually into several. Coding regions begin with the [[start codon]] and end with a [[stop codon]]. In general, the start codon is an AUG triplet and the stop codon is UAG ("amber"), UAA ("ochre"), or UGA ("opal"). The coding regions tend to be stabilised by internal base pairs; this impedes degradation.<ref>{{cite journal | vauthors = Shabalina SA, Ogurtsov AY, Spiridonov NA | title = A periodic pattern of mRNA secondary structure created by the genetic code | journal = Nucleic Acids Research | volume = 34 | issue = 8 | pages = 2428–2437 | year = 2006 | pmid = 16682450 | pmc = 1458515 | doi = 10.1093/nar/gkl287 }}</ref><ref>{{cite journal | vauthors = Katz L, Burge CB | title = Widespread selection for local RNA secondary structure in coding regions of bacterial genes | journal = Genome Research | volume = 13 | issue = 9 | pages = 2042–2051 | date = September 2003 | pmid = 12952875 | pmc = 403678 | doi = 10.1101/gr.1257503 }}</ref> In addition to being protein-coding, portions of coding regions may serve as regulatory sequences in the [[pre-mRNA]] as [[exonic splicing enhancer]]s or [[exonic splicing silencer]]s.

=== Untranslated regions ===
{{main|5' UTR|3' UTR}}
[[File:Fbioe-09-718753-g002.jpg|thumb|Universal structure of eukaryotic mRNA, showing the structure of the 5' and 3' UTRs.]]
Untranslated regions (UTRs) are sections of the mRNA before the start codon and after the stop codon that are not translated, termed the [[five prime untranslated region]] (5' UTR) and [[three prime untranslated region]] (3' UTR), respectively. These regions are transcribed with the coding region and thus are [[exon]]ic as they are present in the mature mRNA. Several roles in gene expression have been attributed to the untranslated regions, including mRNA stability, mRNA localization, and [[translational efficiency]]. The ability of a UTR to perform these functions depends on the sequence of the UTR and can differ between mRNAs. Genetic variants in 3' UTR have also been implicated in disease susceptibility because of the change in RNA structure and protein translation.<ref>{{cite journal | vauthors = Lu YF, Mauger DM, Goldstein DB, Urban TJ, Weeks KM, Bradrick SS | title = IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance | journal = Scientific Reports | volume = 5 | pages = 16037 | date = November 2015 | pmid = 26531896 | pmc = 4631997 | doi = 10.1038/srep16037 | bibcode = 2015NatSR...516037L }}</ref>

The stability of mRNAs may be controlled by the 5' UTR and/or 3' UTR due to varying affinity for RNA degrading enzymes called [[ribonuclease]]s and for ancillary proteins that can promote or inhibit RNA degradation. (See also, [[C-rich stability element]].)

Translational efficiency, including sometimes the complete inhibition of translation, can be controlled by UTRs. Proteins that bind to either the 3' or 5' UTR may affect translation by influencing the ribosome's ability to bind to the mRNA. [[MicroRNA]]s bound to the [[3' UTR]] also may affect translational efficiency or mRNA stability.

Cytoplasmic localization of mRNA is thought to be a function of the 3' UTR. Proteins that are needed in a particular region of the cell can also be translated there; in such a case, the 3' UTR may contain sequences that allow the transcript to be localized to this region for translation.

Some of the elements contained in untranslated regions form a characteristic [[secondary structure]] when transcribed into RNA. These structural mRNA elements are involved in regulating the mRNA. Some, such as the [[SECIS element]], are targets for proteins to bind. One class of mRNA element, the [[riboswitch]]es, directly bind small molecules, changing their fold to modify levels of transcription or translation. In these cases, the mRNA regulates itself.

===Poly(A) tail===
{{main|Polyadenylation}}
The 3' poly(A) tail is a long sequence of [[adenine]] nucleotides (often several hundred) added to the [[3' end]] of the pre-mRNA. This tail promotes export from the nucleus and translation, and protects the mRNA from degradation.

=== Monocistronic versus polycistronic mRNA ===
{{see also|Cistron}}
An mRNA molecule is said to be monocistronic when it contains the genetic information to [[Translation (genetics)|translate]] only a single [[protein]] chain (polypeptide). This is the case for most of the [[Eukaryote|eukaryotic]] mRNAs.<ref name="Kozak_1983">
{{cite journal | vauthors = Kozak M | title = Comparison of initiation of protein synthesis in procaryotes, eucaryotes, and organelles | journal = Microbiological Reviews | volume = 47 | issue = 1 | pages = 1–45 | date = March 1983 | pmid = 6343825 | pmc = 281560 | doi = 10.1128/MMBR.47.1.1-45.1983}}
</ref><ref>{{cite journal | vauthors = Niehrs C, Pollet N | title = Synexpression groups in eukaryotes | journal = Nature | volume = 402 | issue = 6761 | pages = 483–487 | date = December 1999 | pmid = 10591207 | doi = 10.1038/990025 | bibcode = 1999Natur.402..483N | s2cid = 4349134 }}</ref> On the other hand, polycistronic mRNA carries several [[open reading frame]]s (ORFs), each of which is translated into a polypeptide. These polypeptides usually have a related function (they often are the subunits composing a final complex protein) and their coding sequence is grouped and regulated together in a regulatory region, containing a [[Promoter (biology)|promoter]] and an [[Operator (biology)|operator]]. Most of the mRNA found in [[bacteria]] and [[archaea]] is polycistronic,<ref name="Kozak_1983"/> as is the human mitochondrial genome.<ref name="MercerNeph2011">{{cite journal | vauthors = Mercer TR, Neph S, Dinger ME, Crawford J, Smith MA, Shearwood AM, Haugen E, Bracken CP, Rackham O, Stamatoyannopoulos JA, Filipovska A, Mattick JS |author-link10=John Stamatoyannopoulos | title = The human mitochondrial transcriptome | journal = Cell | volume = 146 | issue = 4 | pages = 645–658 | date = August 2011 | pmid = 21854988 | pmc = 3160626 | doi = 10.1016/j.cell.2011.06.051 }}</ref> Dicistronic or bicistronic mRNA encodes only two [[protein]]s.

=== mRNA circularization ===
[[File:Fgene-10-00006-g001.jpg|thumb|mRNA circularisation and regulation]]
In eukaryotes mRNA molecules form circular structures due to an interaction between the [[eIF4E]] and [[poly(A)-binding protein]], which both bind to [[eIF4G]], forming an mRNA-protein-mRNA bridge.<ref>{{cite journal | vauthors = Wells SE, Hillner PE, Vale RD, Sachs AB | title = Circularization of mRNA by eukaryotic translation initiation factors | journal = Molecular Cell | volume = 2 | issue = 1 | pages = 135–140 | date = July 1998 | pmid = 9702200 | doi = 10.1016/S1097-2765(00)80122-7 | citeseerx = 10.1.1.320.5704 }}</ref> Circularization is thought to promote cycling of ribosomes on the mRNA leading to time-efficient translation, and may also function to ensure only intact mRNA are translated (partially degraded mRNA characteristically have no m7G cap, or no poly-A tail).<ref>{{cite journal | vauthors = López-Lastra M, Rivas A, Barría MI | title = Protein synthesis in eukaryotes: the growing biological relevance of cap-independent translation initiation | journal = Biological Research | volume = 38 | issue = 2–3 | pages = 121–146 | year = 2005 | pmid = 16238092 | doi = 10.4067/S0716-97602005000200003 | doi-access = free }}</ref>

Other mechanisms for circularization exist, particularly in virus mRNA. [[Poliovirus]] mRNA uses a cloverleaf section towards its 5' end to bind PCBP2, which binds [[poly(A)-binding protein]], forming the familiar mRNA-protein-mRNA circle. [[Barley yellow dwarf virus]] has binding between mRNA segments on its 5' end and 3' end (called kissing stem loops), circularizing the mRNA without any proteins involved.

RNA virus genomes (the + strands of which are translated as mRNA) are also commonly circularized.<ref>{{cite journal | vauthors = Zhang X, Liang Z, Wang C, Shen Z, Sun S, Gong C, Hu X | title = Viral Circular RNAs and Their Possible Roles in Virus-Host Interaction | journal = Frontiers in Immunology | volume = 13 | pages = 939768 | date = 2022 | pmid = 35784275 | pmc = 9247149 | doi = 10.3389/fimmu.2022.939768 | doi-access = free }}</ref> During genome replication the circularization acts to enhance genome replication speeds, cycling viral RNA-dependent RNA polymerase much the same as the ribosome is hypothesized to cycle.

==Degradation==
Different mRNAs within the same cell have distinct lifetimes (stabilities). In bacterial cells, individual mRNAs can survive from seconds to more than an hour. However, the lifetime averages between 1 and 3 minutes, making bacterial mRNA much less stable than eukaryotic mRNA.<ref>{{Cite book|title=Lewin's genes X|date=2011|publisher=Jones and Bartlett| veditors = Lewin B, Krebs JE, Kilpatrick ST, Goldstein ES |editor-link1=Benjamin Lewin |isbn=9780763766320|edition=10th|location=Sudbury, Mass.|oclc=456641931|url-access=registration|url=https://archive.org/details/lewinsgenesx0000unse}}</ref> In mammalian cells, mRNA lifetimes range from several minutes to days.<ref>{{cite journal | vauthors = Yu J, Russell JE | title = Structural and functional analysis of an mRNP complex that mediates the high stability of human beta-globin mRNA | journal = Molecular and Cellular Biology | volume = 21 | issue = 17 | pages = 5879–5888 | date = September 2001 | pmid = 11486027 | pmc = 87307 | doi = 10.1128/mcb.21.17.5879-5888.2001 }}</ref> The greater the stability of an mRNA the more protein may be produced from that mRNA. The limited lifetime of mRNA enables a cell to alter protein synthesis rapidly in response to its changing needs. There are many mechanisms that lead to the destruction of an mRNA, some of which are described below.

===Prokaryotic mRNA degradation===
[[File:1-s2.0-S1874939913000436-gr1 lrg.jpg|thumb|Overview of mRNA decay pathways in the different life domains.]]
In general, in prokaryotes the lifetime of mRNA is much shorter than in eukaryotes. Prokaryotes degrade messages by using a combination of ribonucleases, including [[endonuclease]]s, 3' [[exonuclease]]s, and 5' exonucleases. In some instances, [[small RNA|small RNA molecules]] (sRNA) tens to hundreds of nucleotides long can stimulate the degradation of specific mRNAs by base-pairing with complementary sequences and facilitating ribonuclease cleavage by [[RNase III]]. It was recently shown that bacteria also have a sort of [[5' cap]] consisting of a triphosphate on the [[5' end]].<ref name=Deana2008>{{cite journal | vauthors = Deana A, Celesnik H, Belasco JG | title = The bacterial enzyme RppH triggers messenger RNA degradation by 5' pyrophosphate removal | journal = Nature | volume = 451 | issue = 7176 | pages = 355–358 | date = January 2008 | pmid = 18202662 | doi = 10.1038/nature06475 | bibcode = 2008Natur.451..355D | s2cid = 4321451 }}</ref> Removal of two of the phosphates leaves a 5' monophosphate, causing the message to be destroyed by the exonuclease RNase J, which degrades 5' to 3'.

===Eukaryotic mRNA turnover===
Inside eukaryotic cells, there is a balance between the processes of [[Translation (genetics)|translation]] and mRNA decay. Messages that are being actively translated are bound by [[ribosome]]s, the [[eukaryotic initiation factor]]s [[eIF-4E]] and [[eIF-4G]], and [[poly(A)-binding protein]]. eIF-4E and eIF-4G block the decapping enzyme ([[DCP2]]), and poly(A)-binding protein blocks the [[exosome complex]], protecting the ends of the message. The balance between translation and decay is reflected in the size and abundance of cytoplasmic structures known as [[P-bodies]].<ref name=Parker2007>{{cite journal | vauthors = Parker R, Sheth U | title = P bodies and the control of mRNA translation and degradation | journal = Molecular Cell | volume = 25 | issue = 5 | pages = 635–646 | date = March 2007 | pmid = 17349952 | doi = 10.1016/j.molcel.2007.02.011 | doi-access = free }}</ref> The [[polyadenylation|poly(A) tail]] of the mRNA is shortened by specialized exonucleases that are targeted to specific messenger RNAs by a combination of cis-regulatory sequences on the RNA and trans-acting RNA-binding proteins. Poly(A) tail removal is thought to disrupt the circular structure of the message and destabilize the [[cap binding complex]]. The message is then subject to degradation by either the [[exosome complex]] or the [[decapping complex]]. In this way, translationally inactive messages can be destroyed quickly, while active messages remain intact. The mechanism by which translation stops and the message is handed-off to decay complexes is not understood in detail. The majority of mRNA decay was believed to be cytoplasmic; however, recently, a novel mRNA decay pathway was described, which starts in the nucleus.<ref name=Chattopadhyay2022>{{cite journal | vauthors = Chattopadhyay S, Garcia Martinez J, Haimovich G, Fischer J, Khwaja A, Barkai O, Chuartzman SG, Schuldiner M, Elran R, Rosenberg M, Urim S, Deshmukh S, Bohnsack K, Bohnsack M, Perez Ortin J, Choder M | title = RNA-controlled nucleocytoplasmic shuttling of mRNA decay factors regulates mRNA synthesis and a novel mRNA decay pathway | journal = Nature Communications | volume = 13(1): 7184 | date = November 2022 | issue = 1 | page = 7184 | pmid = 36418294 | doi = 10.1038/s41467-022-34417-z | doi-access = free | pmc = 9684461 | bibcode = 2022NatCo..13.7184C }}</ref>

===AU-rich element decay===
The presence of [[AU-rich element]]s in some mammalian mRNAs tends to destabilize those transcripts through the action of cellular proteins that bind these sequences and stimulate [[poly(A)]] tail removal. Loss of the poly(A) tail is thought to promote mRNA degradation by facilitating attack by both the [[exosome complex]]<ref name=Chen2001>{{cite journal | vauthors = Chen CY, Gherzi R, Ong SE, Chan EL, Raijmakers R, Pruijn GJ, Stoecklin G, Moroni C, Mann M, Karin M | title = AU binding proteins recruit the exosome to degrade ARE-containing mRNAs | journal = Cell | volume = 107 | issue = 4 | pages = 451–464 | date = November 2001 | pmid = 11719186 | doi = 10.1016/S0092-8674(01)00578-5 | s2cid = 14817671 | doi-access = free }}</ref> and the [[decapping complex]].<ref>{{cite journal | vauthors = Fenger-Grøn M, Fillman C, Norrild B, Lykke-Andersen J | title = Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping | journal = Molecular Cell | volume = 20 | issue = 6 | pages = 905–915 | date = December 2005 | pmid = 16364915 | doi = 10.1016/j.molcel.2005.10.031 | doi-access = free }}</ref> Rapid mRNA degradation via [[AU-rich element]]s is a critical mechanism for preventing the overproduction of potent cytokines such as tumor necrosis factor (TNF) and granulocyte-macrophage colony stimulating factor (GM-CSF).<ref name="Shaw1986">{{cite journal | vauthors = Shaw G, Kamen R | title = A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation | journal = Cell | volume = 46 | issue = 5 | pages = 659–667 | date = August 1986 | pmid = 3488815 | doi = 10.1016/0092-8674(86)90341-7 | s2cid = 40332253 }}</ref> AU-rich elements also regulate the biosynthesis of proto-oncogenic transcription factors like [[c-Jun]] and [[c-Fos]].<ref name=Chen1995>{{cite journal | vauthors = Chen CY, Shyu AB | title = AU-rich elements: characterization and importance in mRNA degradation | journal = Trends in Biochemical Sciences | volume = 20 | issue = 11 | pages = 465–470 | date = November 1995 | pmid = 8578590 | doi = 10.1016/S0968-0004(00)89102-1 }}</ref>

===Nonsense-mediated decay===
{{main|Nonsense-mediated decay}}

Eukaryotic messages are subject to surveillance by [[nonsense-mediated decay]] (NMD), which checks for the presence of premature stop codons (nonsense codons) in the message. These can arise via incomplete splicing, [[V(D)J recombination]] in the [[adaptive immune system]], mutations in DNA, transcription errors, [[leaky scanning]] by the ribosome causing a [[frame shift]], and other causes. Detection of a premature stop codon triggers mRNA degradation by 5' decapping, 3' [[poly(A)]] tail removal, or [[endonuclease|endonucleolytic cleavage]].<ref name=Isken2007>{{cite journal | vauthors = Isken O, Maquat LE | title = Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function | journal = Genes & Development | volume = 21 | issue = 15 | pages = 1833–1856 | date = August 2007 | pmid = 17671086 | doi = 10.1101/gad.1566807 | doi-access = free }}</ref>

===Small interfering RNA (siRNA)===
{{main|siRNA}}

In [[metazoan]]s, [[small interfering RNA]]s (siRNAs) processed by [[Dicer]] are incorporated into a complex known as the [[RNA-induced silencing complex]] or RISC. This complex contains an [[endonuclease]] that cleaves perfectly complementary messages to which the siRNA binds. The resulting mRNA fragments are then destroyed by [[exonuclease]]s. siRNA is commonly used in laboratories to block the function of genes in cell culture. It is thought to be part of the innate immune system as a defense against double-stranded RNA viruses.<ref name=Obbard2009>{{cite journal | vauthors = Obbard DJ, Gordon KH, Buck AH, Jiggins FM | title = The evolution of RNAi as a defence against viruses and transposable elements | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 364 | issue = 1513 | pages = 99–115 | date = January 2009 | pmid = 18926973 | pmc = 2592633 | doi = 10.1098/rstb.2008.0168 }}</ref>

===MicroRNA (miRNA)===
{{main|microRNA}}

MicroRNAs (miRNAs) are small RNAs that typically are partially complementary to sequences in metazoan messenger RNAs.<ref>Robert E. Farrell, Jr. RNA Methodologies, 5th Edition. Academic Press, 2017</ref><ref>{{cite journal | vauthors = Brennecke J, Stark A, Russell RB, Cohen SM | title = Principles of microRNA-target recognition | journal = PLOS Biology | volume = 3 | issue = 3 | pages = e85 | date = March 2005 | pmid = 15723116 | pmc = 1043860 | doi = 10.1371/journal.pbio.0030085 | doi-access = free }}</ref> Binding of a miRNA to a message can repress translation of that message and accelerate poly(A) tail removal, thereby hastening mRNA degradation. The mechanism of action of miRNAs is the subject of active research.<ref>Tasuku Honjo, Michael Reth, Andreas Radbruch, Frederick Alt. Molecular Biology of B Cells, 2nd Edition. Academic Press, 2014 (including "updated research on microRNAs")</ref><ref name=Eulalio2009>{{cite journal | vauthors = Eulalio A, Huntzinger E, Nishihara T, Rehwinkel J, Fauser M, Izaurralde E | title = Deadenylation is a widespread effect of miRNA regulation | journal = RNA | volume = 15 | issue = 1 | pages = 21–32 | date = January 2009 | pmid = 19029310 | pmc = 2612776 | doi = 10.1261/rna.1399509 }}</ref>

===Other decay mechanisms===
There are other ways by which messages can be degraded, including [[non-stop decay]] and silencing by [[Piwi-interacting RNA]] (piRNA), among others.

== Applications ==
{{see also|mRNA vaccine|RNA therapeutics}}
The administration of a [[nucleoside-modified messenger RNA]] sequence can cause a cell to make a protein, which in turn could directly treat a disease or could function as a [[vaccine]]; more indirectly the protein could drive an endogenous [[stem cell]] to differentiate in a desired way.<ref name=NatRevMat>{{cite journal| vauthors = Hajj KA, Whitehead KA |title=Tools for translation: non-viral materials for therapeutic mRNA delivery|journal=Nature Reviews Materials|date=12 September 2017|volume=2|issue=10|pages=17056|doi=10.1038/natrevmats.2017.56|bibcode=2017NatRM...217056H|doi-access=free}}</ref><ref name="GEN">{{cite news| vauthors = Gousseinov E, Kozlov M, Scanlan C |title=RNA-Based Therapeutics and Vaccines|url=https://www.genengnews.com/gen-exclusives/rna-based-therapeutics-and-vaccines/77900520|work=Genetic Engineering News|date=September 15, 2015}}</ref>

The primary challenges of RNA therapy center on delivering the RNA to the appropriate cells.<ref name="genemed">{{cite journal|vauthors=Kaczmarek JC, Kowalski PS, Anderson DG|date=June 2017|title=Advances in the delivery of RNA therapeutics: from concept to clinical reality|journal=Genome Medicine|volume=9|issue=1|pages=60|doi=10.1186/s13073-017-0450-0|pmc=5485616|pmid=28655327 |doi-access=free }}</ref> Challenges include the fact that naked RNA sequences naturally degrade after preparation; they may trigger the body's [[immune system]] to attack them as an invader; and they are [[Semipermeable membrane|impermeable]] to the [[cell membrane]].<ref name="GEN"/> Once within the cell, they must then leave the cell's transport mechanism to take action within the [[cytoplasm]], which houses the necessary [[ribosomes]].<ref name=NatRevMat/>

Overcoming these challenges, mRNA as a therapeutic was first put forward in 1989 "after the development of a broadly applicable in vitro transfection technique."<ref>{{cite journal | vauthors = Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ | title = Developing mRNA-vaccine technologies | journal = RNA Biology | volume = 9 | issue = 11 | pages = 1319–30 | date = November 2012 | pmid = 23064118 | pmc = 3597572 | doi = 10.4161/rna.22269 }}</ref> In the 1990s, mRNA vaccines for personalized cancer have been developed, relying on non-nucleoside modified mRNA. mRNA based therapies continue to be investigated as a method of treatment or therapy for both cancer as well as auto-immune, metabolic, and respiratory inflammatory diseases. Gene editing therapies such as [[CRISPR gene editing|CRISPR]] may also benefit from using mRNA to induce cells to make the desired [[Cas9|Cas]] protein.<ref>{{Cite web| vauthors = Haridi R |date=2021-04-23|title=The mRNA revolution: How COVID-19 hit fast-forward on an experimental technology|url=https://newatlas.com/science/mrna-revolution-vaccine-covid-therapy-pandemic-future-cancer/|access-date=2021-04-26|website=New Atlas|language=en-US}}</ref>

Since the 2010s, RNA vaccines and other RNA therapeutics have been considered to be "a new class of drugs".<ref>{{Citation|title=mRNA-based therapeutics–developing a new class of drugs.|date=2014|work=[[Nature Reviews Drug Discovery]]|volume=13|issue=10|pages=759–780|language=en|pmid=25150148|vauthors=Kowalska J, Wypijewska del Nogal A, Darzynkiewicz ZM, Buck J, Nicola C, Kuhn AN, Lukaszewicz M, Zuberek J, Strenkowska M, Ziemniak M, Maciejczyk M, Bojarska E, Rhoads RE, Darzynkiewicz E, Sahin U, Jemielity J |doi=10.1093/nar/gku757 |doi-access=free |pmc=4176373}}</ref> The first mRNA-based vaccines received restricted authorization and were rolled out across the world during the [[COVID-19 pandemic]] by [[Pfizer–BioNTech COVID-19 vaccine]] and [[Moderna COVID-19 vaccine|Moderna]], for example.<ref name="pmid35534554">{{cite journal | vauthors = Barbier AJ, Jiang AY, Zhang P, Wooster R, Anderson DG | title = The clinical progress of mRNA vaccines and immunotherapies | journal = Nature Biotechnology | volume = 40 | issue = 6 | pages = 840–854 | date = June 2022 | pmid = 35534554 | doi = 10.1038/s41587-022-01294-2 | s2cid = 248667843 | doi-access = free }}</ref>
The 2023 [[Nobel Prize in Physiology or Medicine]] was awarded to [[Katalin Karikó]] and [[Drew Weissman]] for the development of effective mRNA vaccines against COVID-19.<ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 2023 |url=https://www.nobelprize.org/prizes/medicine/2023/press-release/ |access-date=2023-10-03 |website=NobelPrize.org |language=en-US}}</ref><ref>{{Cite news |date=2023-10-02 |title=Hungarian and US scientists win Nobel for COVID-19 vaccine discoveries |language=en |work=Reuters |url=https://www.reuters.com/article/nobel-prize-medicine-idCAKCN3120KJ |access-date=2023-10-03}}</ref><ref>{{Cite web |title=The Nobel Prize in Physiology or Medicine 2023 |url=https://www.nobelprize.org/prizes/medicine/2023/kariko/facts/ |access-date=2023-10-03 |website=NobelPrize.org |language=en-US}}</ref>

== History ==
Several molecular biology studies during the 1950s indicated that RNA played some kind of role in protein synthesis, but that role was not clearly understood. For instance, in one of the earliest reports, [[Jacques Monod]] and his team showed that RNA synthesis was necessary for protein synthesis, specifically during the production of the enzyme [[β-galactosidase]] in the bacterium ''[[Escherichia coli|E. coli]]''.<ref>{{Cite journal | vauthors = Monod J, Pappenheimer AM, Cohen-Bazire G |date=1952 |title=La cinétique de la biosynthèse de la β-galactosidase chez E. coli considérée comme fonction de la croissance  |journal=Biochimica et Biophysica Acta |language=fr |volume=9 |issue=6 |pages=648–660 |doi=10.1016/0006-3002(52)90227-8|pmid=13032175 }}</ref> [[Arthur Pardee]] also found similar RNA accumulation in 1954''.''<ref>{{cite journal | vauthors = Pardee AB | title = Nucleic Acid Precursors and Protein Synthesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 40 | issue = 5 | pages = 263–270 | date = May 1954 | pmid = 16589470 | pmc = 534118 | doi = 10.1073/pnas.40.5.263 | bibcode = 1954PNAS...40..263P | doi-access = free }}</ref> In 1953, [[Alfred Hershey]], June Dixon, and [[Martha Chase]] described a certain cytosine-containing DNA (indicating it was RNA) that disappeared quickly after its synthesis in ''E. coli''.<ref>{{cite journal | vauthors = Hershey AD, Dixon J, Chase M | title = Nucleic acid economy in bacteria infected with bacteriophage T2. I. Purine and pyrimidine composition | journal = The Journal of General Physiology | volume = 36 | issue = 6 | pages = 777–789 | date = July 1953 | pmid = 13069681 | pmc = 2147416 | doi = 10.1085/jgp.36.6.777 }}</ref> In hindsight, this may have been one of the first observations of the existence of mRNA but it was not recognized at the time as such.<ref name="Cobb">{{cite journal |author-link1=Matthew Cobb |vauthors=Cobb M |date=29 June 2015 |title=Who discovered messenger RNA? |journal=Current Biology |volume=25 |issue=13 |pages=R526–R532 |doi=10.1016/j.cub.2015.05.032 |pmid=26126273 |doi-access=free|bibcode=2015CBio...25.R526C }}</ref>

The idea of mRNA was first conceived by [[Sydney Brenner]] and [[Francis Crick]] on 15 April 1960 at [[King's College, Cambridge]], while [[François Jacob]] was telling them about a recent experiment conducted by [[Arthur Pardee]], himself, and Monod (the so-called PaJaMo experiment, which did not prove mRNA existed but suggested the possibility of its existence). With Crick's encouragement, Brenner and Jacob immediately set out to test this new hypothesis, and they contacted [[Matthew Meselson]] at the [[California Institute of Technology]] for assistance. During the summer of 1960, Brenner, Jacob, and Meselson conducted an experiment in Meselson's laboratory at Caltech which was the first to prove the existence of mRNA. That fall, Jacob and Monod coined the name "messenger RNA" and developed the first theoretical framework to explain its function.<ref name="Cobb" />

In February 1961, [[James Watson]] revealed that his [[Harvard University|Harvard]]-based research group had been right behind them with a series of experiments whose results pointed in roughly the same direction. Brenner and the others agreed to Watson's request to delay publication of their research findings. As a result, the Brenner and Watson articles were published simultaneously in the same issue of ''[[Nature (journal)|Nature]]'' in May 1961, while that same month, Jacob and Monod published their theoretical framework for mRNA in the ''[[Journal of Molecular Biology]]''.<ref name="Cobb" />

== See also ==
* [[Extension Poly(A) Test]]
* [[GeneCalling]], an mRNA profiling technology
* [[Missense mRNA]]
* [[mRNA display]]
* [[mRNA surveillance]]
* [[Prokaryotic mRNA degradation]]
* [[Transcriptome]], the sum of all RNA in a cell
* [[modRNA]] Nucleoside-modified messenger RNA

== References ==
{{reflist}}

=== Further reading ===
{{refbegin}}
* {{cite journal | vauthors = Alsaweed M, Lai CT, Hartmann PE, Geddes DT, Kakulas F | title = Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 20680 | date = February 2016 | pmid = 26854194 | pmc = 4745068 | doi = 10.1038/srep20680 | bibcode = 2016NatSR...620680A }}
* {{cite journal | vauthors = [[Karen A. Lillycrop|Lillycrop KA]], Burdge GC | title = Epigenetic mechanisms linking early nutrition to long term health | journal = Best Practice & Research. Clinical Endocrinology & Metabolism | volume = 26 | issue = 5 | pages = 667–676 | date = October 2012 | pmid = 22980048 | doi = 10.1016/j.beem.2012.03.009 }}
* {{cite journal | vauthors = Melnik BC, Kakulas F, Geddes DT, Hartmann PE, John SM, Carrera-Bastos P, Cordain L, Schmitz G | title = Milk miRNAs: simple nutrients or systemic functional regulators? | journal = Nutrition & Metabolism | volume = 13 | issue = 1 | pages = 42 | date = 21 June 2016 | pmid = 27330539 | pmc = 4915038 | doi = 10.1186/s12986-016-0101-2 | doi-access = free }}
* {{cite journal | vauthors = Vickers MH | title = Early life nutrition, epigenetics and programming of later life disease | journal = Nutrients | volume = 6 | issue = 6 | pages = 2165–2178 | date = June 2014 | pmid = 24892374 | pmc = 4073141 | doi = 10.3390/nu6062165 | doi-access = free }}
* {{cite journal | vauthors = Zhou Q, Li M, Wang X, Li Q, Wang T, Zhu Q, Zhou X, Wang X, Gao X, Li X | title = Immune-related microRNAs are abundant in breast milk exosomes | journal = International Journal of Biological Sciences | volume = 8 | issue = 1 | pages = 118–123 | date = 2012 | pmid = 22211110 | pmc = 3248653 | doi = 10.7150/ijbs.8.118 }}
* {{cite journal | vauthors = Krause W | title = mRNA — From COVID-19 Treatment to Cancer Immunotherapy | journal = Biomedicines | volume = 11 | issue = 2 | pages = 308 | date = 2023 | pmid = 36830845 | pmc = 9953480| doi = 10.3390/biomedicines11020308 |doi-access=free}}
{{refend}}

== External links ==
{{scholia}}
{{Commons category|MRNA|lcfirst=yes}}
* [https://web.archive.org/web/20150210230607/http://rnaiatlas.ethz.ch/ RNAi Atlas]: a database of RNAi libraries and their target analysis results
* [http://www.exiqon.com/mirsearch miRSearch] {{Webarchive|url=https://web.archive.org/web/20121204141531/http://www.exiqon.com/mirsearch |date=2012-12-04 }}: Tool for finding microRNAs that target mRNA
* [https://www.youtube.com/watch?v=m95RO6Df_SI How mRNA is coded?]: YouTube video
* [https://theconversation.com/what-is-mrna-the-messenger-molecule-thats-been-in-every-living-cell-for-billions-of-years-is-the-key-ingredient-in-some-covid-19-vaccines-158511 What is mRNA?]: theconversation.com

{{Nucleic acids}}
{{Gene expression}}

[[Category:RNA]]
[[Category:Gene expression]]
[[Category:Protein biosynthesis]]
[[Category:Molecular genetics]]
[[Category:Spliceosome]]
[[Category:RNA splicing]]
[[Category:Life sciences industry]]