Editing Reverse transcriptase

{{Short description|Enzyme which generates DNA}}
{{Infobox protein family
| Symbol = RVT_1
| Name = Reverse transcriptase<br />(RNA-dependent DNA polymerase)
| image = Reverse transcriptase 3KLF labels.png
| width =
| caption = Crystallographic structure of [[HIV]]-1 reverse transcriptase where the two subunits p51 and p66 are colored and the active sites of polymerase and nuclease are highlighted.<ref name="pmid20852643">{{PDB|3KLF}}; {{cite journal | vauthors = Tu X, Das K, Han Q, Bauman JD, Clark AD, Hou X, Frenkel YV, Gaffney BL, Jones RA, Boyer PL, Hughes SH, Sarafianos SG, Arnold E | title = Structural basis of HIV-1 resistance to AZT by excision | journal = Nature Structural & Molecular Biology | volume = 17 | issue = 10 | pages = 1202–9 | date = October 2010 | pmid = 20852643 | pmc = 2987654 | doi = 10.1038/nsmb.1908 }}</ref>
| Pfam = PF00078
| Pfam_clan = CL0027
| InterPro = IPR000477
| SMART =
| PROSITE = PS50878
| SCOP = 1hmv
| TCDB =
| OPM family =
| OPM protein =
| CDD = cd00304
}}
{{infobox enzyme
| Name       = RNA-directed DNA polymerase
| EC_number  = 2.7.7.49
| CAS_number = 9068-38-6
| GO_code    = 0003964
| image      =
| width      =
| caption    = 
}}

A '''reverse transcriptase''' ('''RT''') is an [[enzyme]] used to convert [[RNA genome]] to [[DNA]], a process termed '''reverse transcription'''. Reverse transcriptases are used by [[virus]]es such as [[HIV]] and [[hepatitis B virus|hepatitis B]] to replicate their genomes, by  [[retrotransposon]] mobile genetic elements to proliferate within the host genome, and by [[eukaryote|eukaryotic]] cells to extend the [[telomeres]] at the ends of their [[Chromosome#Eukaryotes|linear chromosomes]]. The process does not violate the flows of genetic information as described by the classical [[central dogma of molecular biology|central dogma]], but rather expands it to include transfers of information from RNA to DNA.<ref name = "Crick_1970">{{cite journal | vauthors = Crick F | title = Central dogma of molecular biology | journal = Nature | volume = 227 | issue = 5258 | pages = 561–3 | date = August 1970 | pmid = 4913914 | doi = 10.1038/227561a0 | s2cid = 4164029 | bibcode = 1970Natur.227..561C }}</ref><ref>{{cite book | vauthors = Sarkar S |title=The Philosophy and History of Molecular Biology: New Perspectives |date=1996 |publisher=Kluwer Academic Publishers |location=Dordrecht |pages=187–232}}</ref><ref>{{cite journal | vauthors = Danchin É, Pocheville A, Rey O, Pujol B, Blanchet S |title=Epigenetically facilitated mutational assimilation: epigenetics as a hub within the inclusive evolutionary synthesis |journal=Biological Reviews |date=2019 |volume=94 |issue=1 |pages=259–282 |doi=10.1111/brv.12453 |pmc=6378602|s2cid=67861162 |doi-access=free }}</ref>

Retroviral RT has three sequential biochemical activities: RNA-dependent [[DNA polymerase]] activity, [[ribonuclease H]] (RNase H), and DNA-dependent DNA polymerase activity. Collectively, these activities enable the enzyme to convert single-stranded RNA into double-stranded cDNA. In retroviruses and retrotransposons, this cDNA can then integrate into the host genome, from which new RNA copies can be made via host-cell [[transcription (biology)|transcription]]. The same sequence of reactions is widely used in the laboratory to convert RNA to DNA for use in [[molecular cloning]], [[RNA sequencing]], [[polymerase chain reaction]] (PCR), or [[DNA microarray|genome analysis]].

== History ==
Reverse transcriptases were discovered by [[Howard Temin]] at the [[University of Wisconsin–Madison]] in ''[[Rous sarcoma virus|Rous sarcoma]]'' virions<ref name="pmid4316301">{{cite journal | vauthors = Temin HM, Mizutani S | title = RNA-dependent DNA polymerase in virions of Rous sarcoma virus | journal = Nature | volume = 226 | issue = 5252 | pages = 1211–3 | date = June 1970 | pmid = 4316301 | doi = 10.1038/2261211a0 | s2cid = 4187764 }}</ref> and independently isolated by [[David Baltimore]] in 1970 at [[MIT]] from two RNA tumour viruses: [[murine leukemia virus]] and again [[Rous sarcoma virus]].<ref name="pmid4316300">{{cite journal | vauthors = Baltimore D | title = RNA-dependent DNA polymerase in virions of RNA tumour viruses | journal = Nature | volume = 226 | issue = 5252 | pages = 1209–11 | date = June 1970 | pmid = 4316300 | doi = 10.1038/2261209a0 | s2cid = 4222378 }}</ref> For their achievements, they shared the 1975 [[Nobel Prize in Physiology or Medicine]] (with [[Renato Dulbecco]]).

Well-studied reverse transcriptases include:
* HIV-1 reverse transcriptase from [[HIV|human immunodeficiency virus]] type 1 ({{PDB|1HMV}}) has two subunits, which have respective molecular weights of 66 and 51 [[kilodalton|kDas]].<ref>{{cite journal | vauthors = Ferris AL, Hizi A, Showalter SD, Pichuantes S, Babe L, Craik CS, Hughes SH | title = Immunologic and proteolytic analysis of HIV-1 reverse transcriptase structure | journal = Virology | volume = 175 | issue = 2 | pages = 456–64 | date = April 1990 | pmid = 1691562 | doi = 10.1016/0042-6822(90)90430-y | url = http://www.craiklab.ucsf.edu/docs/pub47.pdf }}</ref>
* M-MLV reverse transcriptase from the [[murine leukemia virus|Moloney murine leukemia virus]] is a single 75 kDa monomer.<ref name="Konishi_2012">{{cite journal | vauthors = Konishi A, Yasukawa K, Inouye K | title = Improving the thermal stability of avian myeloblastosis virus reverse transcriptase α-subunit by site-directed mutagenesis | journal = Biotechnology Letters | volume = 34 | issue = 7 | pages = 1209–15 | date = July 2012 | pmid = 22426840 | doi = 10.1007/s10529-012-0904-9 | hdl = 2433/157247 | s2cid = 207096569 | url = http://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/157247/1/s10529-012-0904-9.pdf | hdl-access = free }}</ref>
* AMV reverse transcriptase from the [[Alpharetrovirus|avian myeloblastosis virus]] also has two subunits, a 63 kDa subunit and a 95 kDa subunit.<ref name="Konishi_2012"/>
* [[Telomerase reverse transcriptase]] that maintains the [[telomere]]s of [[eukaryotic]] [[chromosomes]].<ref>{{cite journal | vauthors = Autexier C, Lue NF | title = The structure and function of telomerase reverse transcriptase | journal = Annual Review of Biochemistry | volume = 75 | issue = 1 | pages = 493–517 | date = June 2006 | pmid = 16756500 | doi = 10.1146/annurev.biochem.75.103004.142412 }}</ref>

== Function in viruses ==
[[File:HIV-1 Reverse Transcriptase with Active Sites.png|thumb|left|Reverse transcriptase is shown with its finger, palm, and thumb regions. The catalytic [[amino acid]]s of the [[RNase H]] active site and the [[polymerase]] active site are shown in ball-and-stick form.]]
The enzymes are encoded and used by viruses that use reverse transcription as a step in the process of replication. Reverse-transcribing [[RNA virus]]es, such as [[retrovirus]]es, use the enzyme to reverse-transcribe their RNA [[genome]]s into DNA, which is then integrated into the host genome and replicated along with it. Reverse-transcribing [[DNA virus]]es, such as the [[hepadnavirus]]es, can allow RNA to serve as a template in assembling and making DNA strands. HIV infects humans with the use of this enzyme. Without reverse transcriptase, the viral genome would not be able to incorporate into the host cell, resulting in failure to replicate.{{citation needed|date=June 2022}}

===Process of reverse transcription or retrotranscription===
Reverse transcriptase creates double-stranded DNA from an RNA template.

In virus species with reverse transcriptase lacking DNA-dependent DNA polymerase activity, creation of double-stranded DNA can possibly be done by host-encoded [[DNA polymerase δ]], mistaking the viral DNA-RNA for a primer and synthesizing a double-stranded DNA by a similar mechanism as in [[Primer (molecular biology)#Primer removal|primer removal]], where the newly synthesized DNA displaces the original RNA template.{{citation needed|date=June 2022}}

The process of reverse transcription, also called retrotranscription or retrotras, is extremely error-prone, and it is during this step that mutations may occur. Such mutations may cause [[Resistance to antiviral drugs|drug resistance]].{{cn|date=November 2024}}

==== Retroviral reverse transcription ====
[[Image:Reverse transcription.svg|thumb|300px|Mechanism of reverse transcription in HIV. Step numbers will not match up.]]
[[Retroviruses]], also referred to as class VI [[ssRNA-RT]] viruses, are RNA reverse-transcribing viruses with a DNA intermediate. Their genomes consist of two molecules of [[sense (molecular biology)#RNA sense in viruses|positive-sense]] single-stranded RNA with a [[5' cap]] and [[Polyadenylation|3' polyadenylated tail]]. Examples of retroviruses include the human immunodeficiency virus ([[HIV]]) and the human T-lymphotropic virus ([[HTLV]]). Creation of double-stranded DNA occurs in the [[cytosol]]<ref>[http://www.bio-medicine.org/biology-definition/Retrovirus/ Bio-Medicine.org - Retrovirus] Retrieved on 17 Feb, 2009</ref> as a series of these steps:
# [[lysidine (nucleoside)|Lysyl]] [[tRNA]] acts as a primer and hybridizes to a complementary part of the virus RNA genome called the primer binding site or PBS.
# Reverse transcriptase then adds DNA nucleotides onto the 3' end of the primer, synthesizing [[complementary DNA|DNA complementary]] to the U5 (non-coding region) and R region (a direct repeat found at both ends of the RNA molecule) of the viral RNA.
# A domain on the reverse transcriptase enzyme called [[RNAse H]] degrades the U5 and R regions on the 5' end of the RNA.
# The tRNA primer then "jumps" to the 3' end of the viral genome, and the newly synthesised DNA strands hybridizes to the complementary R region on the RNA.
# The complementary DNA (cDNA) added in (2) is further extended.
# The majority of viral RNA is degraded by RNAse H, leaving only the PP sequence.
# Synthesis of the second DNA strand begins, using the remaining PP fragment of viral RNA as a primer.
# The tRNA primer leaves and a "jump" happens. The PBS from the second strand hybridizes with the complementary PBS on the first strand.
# Both strands are extended to form a complete double-stranded DNA copy of the original viral RNA genome, which can then be incorporated into the host's genome by the enzyme [[integrase]].

Creation of double-stranded DNA also involves ''strand transfer'', in which there is a translocation of short DNA product from initial RNA-dependent DNA synthesis to acceptor template regions at the other end of the genome, which are later reached and processed by the reverse transcriptase for its DNA-dependent DNA activity.<ref>{{cite book |vauthors = Telesnitsky A, Goff SP | veditors = Skalka MA, Goff SP | title = Reverse transcriptase| edition = 1st | publisher = Cold Spring Harbor| location = New York | year = 1993 | chapter =  Strong-stop strand transfer during reverse transcription | page = 49| isbn =978-0-87969-382-4 }}</ref>

Retroviral RNA is arranged in 5' terminus to 3' terminus. The site where the [[primer (molecular biology)|primer]] is annealed to viral RNA is called the primer-binding site (PBS). The RNA 5'end to the PBS site is called U5, and the RNA 3' end to the PBS is called the leader. The tRNA primer is unwound between 14 and 22 [[nucleotides]] and forms a base-paired duplex with the viral RNA at PBS. The fact that the PBS is located near the 5' terminus of viral RNA is unusual because reverse transcriptase synthesize DNA from 3' end of the primer in the 5' to 3'  direction (with respect to the newly synthesized DNA strand). Therefore, the primer and reverse transcriptase must be relocated to 3' end of viral RNA. In order to accomplish this reposition, multiple steps and various enzymes including [[DNA polymerase]], ribonuclease H(RNase H) and polynucleotide unwinding are needed.<ref name="isbn0-87969-167-0">{{cite book |vauthors = Bernstein A, Weiss R, Tooze J | title = Molecular Biology of Tumor Viruses | edition = 2nd| publisher = Cold Spring Harbor Laboratory | location = Cold Spring Harbor, N.Y. | year = 1985 | chapter =  RNA tumor viruses }}</ref><ref name="MoellingBroecker2015">{{cite journal | vauthors = Moelling K, Broecker F | title = The reverse transcriptase-RNase H: from viruses to antiviral defense | journal = Annals of the New York Academy of Sciences | volume = 1341 | issue =  1| pages = 126–35 | date = April 2015 | pmid = 25703292 | doi = 10.1111/nyas.12668 | bibcode = 2015NYASA1341..126M | s2cid = 42378727 }}</ref>

The HIV reverse transcriptase also has [[ribonuclease]] activity that degrades the viral RNA during the synthesis of cDNA, as well as [[DNA-dependent DNA polymerase]] activity that copies the [[Sense (molecular biology)|sense]] cDNA strand into an ''antisense'' DNA to form a double-stranded viral DNA intermediate (vDNA).<ref>{{cite web | first = Gary E. | last = Kaiser | name-list-style = vanc | url = http://student.ccbcmd.edu/courses/bio141/lecguide/unit3/viruses/hivlc.html | work = Doc Kaiser's Microbiology Home Page | title = The Life Cycle of HIV | archive-url = https://web.archive.org/web/20100726222939/http://student.ccbcmd.edu/courses/bio141/lecguide/unit3/viruses/hivlc.html | archive-date = 2010-07-26 | url-status = dead | publisher = Community College of Baltimore Count | date = January 2008 }}</ref> The HIV viral RNA structural elements regulate the progression of reverse transcription.<ref name="pmid32916568">{{cite journal | vauthors = Krupkin M, Jackson LN, Ha B, Puglisi EV | title = Advances in understanding the initiation of HIV-1 reverse transcription | journal = Curr Opin Struct Biol | volume = 65 | pages = 175–183 | date = Dec 2020 | pmid = 32916568 | doi = 10.1016/j.sbi.2020.07.005 | pmc = 9973426 | s2cid = 221636459 }}</ref>

== In cellular life ==

Self-replicating stretches of [[eukaryotic]] genomes known as [[retrotransposon]]s utilize reverse transcriptase to move from one position in the genome to another via an RNA intermediate. They are found abundantly in the genomes of plants and animals. [[Telomerase]] is another reverse transcriptase found in many eukaryotes, including humans, which carries its own [[RNA]] template; this RNA is used as a template for [[DNA replication]].<ref name="isbn0-7167-4366-3">{{cite book | vauthors = Krieger M, Scott MP, Matsudaira PT, Lodish HF, Darnell JE, Zipursky L, Kaiser C, Berk A | title = Molecular cell biology | publisher = W.H. Freeman and CO | location = New York | year = 2004 | isbn = 978-0-7167-4366-8 | url-access = registration | url = https://archive.org/details/molecularcellbio00harv }}</ref>

Initial reports of reverse transcriptase in prokaryotes came as far back as 1971 in France ([[Mirko Beljanski|Beljanski]] et al., 1971a, 1972) and a few years later in the USSR (Romashchenko 1977<ref>{{cite journal | vauthors = Romashchenko AG, etal |title=Otdelenie ot preparatov DNK-polimeraz I RNK-zavisimoy DNK-polimeraz; oshistka i svoystva fermenta |journal=[[Proceedings of the USSR Academy of Sciences]] |date=1977 |volume=233 |pages=734–737}}</ref>).  These have since been broadly described as part of bacterial [[Retron]]s, distinct sequences that code for reverse transcriptase, and are used in the synthesis of [[multicopy single-stranded DNA|msDNA]]. In order to initiate synthesis of DNA, a primer is needed. In bacteria, the primer is synthesized during replication.<ref name="pmid4333538">{{cite journal | vauthors = Hurwitz J, Leis JP | title = RNA-dependent DNA polymerase activity of RNA tumor viruses. I. Directing influence of DNA in the reaction | journal = Journal of Virology | volume = 9 | issue = 1 | pages = 116–29 | date = January 1972 | pmid = 4333538 | pmc = 356270 | doi =  10.1128/JVI.9.1.116-129.1972}}</ref>

Valerian Dolja of Oregon State argues that viruses, due to their diversity, have played an evolutionary role in the development of cellular life, with reverse transcriptase playing a central role.<ref>{{cite news | last1 = Arnold | first1 = Carrie | name-list-style = vanc | title = Could Giant Viruses Be the Origin of Life on Earth? | url = http://news.nationalgeographic.com/news/2014/07/140716-giant-viruses-science-life-evolution-origins/ | archive-url = https://web.archive.org/web/20140718130943/http://news.nationalgeographic.com/news/2014/07/140716-giant-viruses-science-life-evolution-origins/ | url-status = dead | archive-date = July 18, 2014 | access-date = 29 May 2016 | work = National Geographic |date=17 July 2014}}</ref>

== Structure ==

The reverse transcriptase employs a "right hand" structure similar to that found in other [[RNA-dependent RNA polymerase|viral nucleic acid polymerase]]s.<ref name="pmid19022262"/><ref name="pmid9309225">{{cite journal | vauthors = Hansen JL, Long AM, Schultz SC | title = Structure of the RNA-dependent RNA polymerase of poliovirus | journal = Structure | volume = 5 | issue = 8 | pages = 1109–22 | date = August 1997 | pmid = 9309225 | doi = 10.1016/S0969-2126(97)00261-X | doi-access = free }}</ref> In addition to the transcription function, retroviral reverse transcriptases have a domain belonging to the [[RNase H]] family, which is vital to their replication. By degrading the RNA template, it allows the other strand of DNA to be synthesized.<ref>{{cite journal | vauthors = Schultz SJ, Champoux JJ | title = RNase H activity: structure, specificity, and function in reverse transcription | journal = Virus Research | volume = 134 | issue = 1–2 | pages = 86–103 | date = June 2008 | pmid = 18261820 | pmc = 2464458 | doi = 10.1016/j.virusres.2007.12.007 }}</ref> Some fragments from the digestion also serve as the primer for the [[DNA polymerase]] (either the same enzyme or a host protein), responsible for making the other (plus) strand.<ref name="pmid19022262">{{cite journal | vauthors = Sarafianos SG, Marchand B, Das K, Himmel DM, Parniak MA, Hughes SH, Arnold E | title = Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition | journal = Journal of Molecular Biology | volume = 385 | issue = 3 | pages = 693–713 | date = January 2009 | pmid = 19022262 | pmc = 2881421 | doi = 10.1016/j.jmb.2008.10.071 }}</ref>

== Replication fidelity ==

There are three different replication systems during the life cycle of a retrovirus. The first process is the reverse transcriptase synthesis of viral DNA from viral RNA, which then forms newly made complementary DNA strands. The second replication process occurs when host cellular DNA polymerase replicates the integrated viral DNA. Lastly, RNA polymerase II transcribes the proviral DNA into RNA, which will be packed into virions. Mutation can occur during one or all of these replication steps.<ref>{{cite book |vauthors = Bbenek K, Kunkel AT| veditors = Skalka MA, Goff PS | title = Reverse transcriptase | publisher = Cold Spring Harbor Laboratory Press | location = New York | year = 1993 | chapter = The fidelity of retroviral reverse transcriptases | page = 85 | isbn = 978-0-87969-382-4 }}</ref>

Reverse transcriptase has a high error rate when transcribing RNA into DNA since, unlike most other [[DNA polymerase]]s, it has no [[Proofreading (biology)|proofreading]] ability. This high error rate allows [[mutation]]s to accumulate at an accelerated rate relative to proofread forms of replication. The commercially available reverse transcriptases produced by [[Promega]] are quoted by their manuals as having error rates in the range of 1 in 17,000 bases for AMV and 1 in 30,000 bases for M-MLV.<ref>{{cite web | url = http://www.promega.com/pnotes/71/7807_22/7807_22_core.pdf | title = Promega kit instruction manual | date = 1999 | archive-url = https://web.archive.org/web/20061121205121/http://www.promega.com/pnotes/71/7807_22/7807_22_core.pdf | archive-date = 2006-11-21 | url-status = dead }}</ref>

Other than creating [[single-nucleotide polymorphism]]s, reverse transcriptases have also been shown to be involved in processes such as [[transcript fusion]]s, [[exon shuffling]] and creating artificial [[antisense]] transcripts.<ref name="pmid20805885">{{cite journal | vauthors = Houseley J, Tollervey D | title = Apparent non-canonical trans-splicing is generated by reverse transcriptase in vitro | journal = PLOS ONE | volume = 5 | issue = 8 | pages = e12271 | date = August 2010 | pmid = 20805885 | pmc = 2923612 | doi = 10.1371/journal.pone.0012271 | bibcode = 2010PLoSO...512271H | doi-access = free }}</ref><ref name="pmid12044895">{{cite journal | vauthors = Zeng XC, Wang SX | title = Evidence that BmTXK beta-BmKCT cDNA from Chinese scorpion Buthus martensii Karsch is an artifact generated in the reverse transcription process | journal = FEBS Letters | volume = 520 | issue = 1–3 | pages = 183–4; author reply 185 | date = June 2002 | pmid = 12044895 | doi = 10.1016/S0014-5793(02)02812-0 | s2cid = 24619868 | doi-access = free }}</ref> It has been speculated that this ''template switching'' activity of reverse transcriptase, which can be demonstrated completely ''in vivo'', may have been one of the causes for finding several thousand unannotated transcripts in the genomes of model organisms.<ref>{{cite journal | title = Response to "The Reality of Pervasive Transcription" | year = 2011  |vauthors = van Bakel H, Nislow C, Blencowe BJ, Hughes TR | journal = PLOS Biology | volume = 9 | issue = 7 | pages = e1001102 | doi = 10.1371/journal.pbio.1001102 | pmc = 3134445 | doi-access = free }}</ref>

===Template switching===

Two [[RNA]] [[genome]]s are packaged into each retrovirus particle, but, after an infection, each virus generates only one [[provirus]].<ref name = Rawson2018>{{cite journal | vauthors = Rawson JM, Nikolaitchik OA, Keele BF, Pathak VK, Hu WS | title = Recombination is required for efficient HIV-1 replication and the maintenance of viral genome integrity | journal = Nucleic Acids Research | volume = 46 | issue = 20 | pages = 10535–10545 | date = November 2018 | pmid = 30307534 | pmc = 6237782 | doi = 10.1093/nar/gky910 }}</ref>  After infection, reverse transcription is accompanied by template switching between the two genome copies (copy choice recombination).<ref name = Rawson2018/>  There are two models that suggest why RNA transcriptase switches templates. The first, the forced copy-choice model, proposes that reverse transcriptase changes the RNA template when it encounters a nick, implying that recombination is obligatory to maintaining virus genome integrity. The second, the dynamic choice model, suggests that reverse transcriptase changes templates when the RNAse function and the polymerase function are not in sync rate-wise, implying that recombination occurs at random and is not in response to genomic damage. A study by Rawson et al. supported both models of recombination.<ref name = Rawson2018 /> From 5 to 14 recombination events per genome occur at each replication cycle.<ref name="pmid26691546">{{cite journal | vauthors = Cromer D, Grimm AJ, Schlub TE, Mak J, Davenport MP | title = Estimating the in-vivo HIV template switching and recombination rate | journal = AIDS | volume = 30 | issue = 2 | pages = 185–92 | date = January 2016 | pmid = 26691546 | doi = 10.1097/QAD.0000000000000936 | s2cid = 20086739 | doi-access = free }}</ref>  Template switching (recombination) appears to be necessary for maintaining genome integrity and as a repair mechanism for salvaging damaged genomes.<ref name="pmid1700865">{{cite journal | vauthors = Hu WS, Temin HM | title = Retroviral recombination and reverse transcription | journal = Science | location = New York, N.Y. | volume = 250 | issue = 4985 | pages = 1227–33 | date = November 1990 | pmid = 1700865 | doi = 10.1126/science.1700865 | bibcode = 1990Sci...250.1227H }}</ref><ref name="Rawson2018" />

==Applications==
[[Image:Zidovudine.svg|thumb|200px|The molecular structure of [[zidovudine]] (AZT), a drug used to inhibit reverse transcriptase ]]

=== Antiviral drugs ===
{{further|Reverse-transcriptase inhibitor}}
As [[HIV]] uses reverse transcriptase to copy its genetic material and generate new viruses (part of a retrovirus proliferation circle), specific drugs have been designed to disrupt the process and thereby suppress its growth. Collectively, these drugs are known as [[reverse-transcriptase inhibitor]]s and include the nucleoside and nucleotide analogues [[zidovudine]] (trade name Retrovir), [[lamivudine]] (Epivir) and [[tenofovir]] (Viread), as well as non-nucleoside inhibitors, such as [[nevirapine]] (Viramune).{{citation needed|date=June 2022}}

=== Molecular biology ===
{{further|Reverse transcription polymerase chain reaction}}
Reverse transcriptase is commonly used in research to apply the [[polymerase chain reaction]] technique to [[RNA]] in a technique called [[reverse transcription polymerase chain reaction]] (RT-PCR).  The classical [[polymerase chain reaction|PCR]] technique can be applied only to [[DNA]] strands, but, with the help of reverse transcriptase, RNA can be transcribed into DNA, thus making [[Polymerase chain reaction|PCR]] analysis of RNA molecules possible. Reverse transcriptase is used also to create [[cDNA library|cDNA libraries]] from [[mRNA]]. The commercial availability of reverse transcriptase greatly improved knowledge in the area of molecular biology, as, along with other [[enzymes]], it allowed scientists to clone, sequence, and characterise RNA.{{cn|date=November 2024}}

== See also ==
{{Portal|Biology|Viruses}}
* [[cDNA library]]
* [[DNA polymerase]]
* [[msDNA]]
* [[Reverse transcribing virus (disambiguation)|Reverse transcribing virus]]<!--intentional link to DAB page-->
* [[RNA polymerase]]
* [[Telomerase]]
* [[Retrotransposon marker]]

== References ==
{{Reflist|32em}}

== External links ==
* {{MeshName|RNA+Transcriptase}}
* [https://web.archive.org/web/20060517042722/http://www.tibotec.com/bgdisplay.jhtml?itemname=HIV_discovery&product=none&s=2 animation of reverse transcriptase action and three reverse transcriptase inhibitors]
* [http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb33_1.html Molecule of the month] (September 2002) at the RCSB PDB
* [https://www.youtube.com/watch?v=RO8MP3wMvqg HIV Replication 3D Medical Animation. (Nov 2008). Video by Boehringer Ingelheim.]
* {{ cite web | url= http://www.rcsb.org/pdb/101/motm.do?momID=33 | title= Molecule of the Month: Reverse Transcriptase (Sep 2002)|access-date= 2013-01-13 | vauthors = Goodsell DS | publisher=  Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB) }}
* {{PDBe-KB2|P03366|Human immunodeficiency virus Reverse transcriptase}}
* [https://www.microbe.tv/twiv/twiv-904/ TWiV 904: 50 years of reverse transcriptase] [[Vincent Racaniello]] travels to [[Cold Spring Harbor Laboratory]] to speak with [[David Baltimore]], [[John Coffin (scientist)]], and [[Harold Varmus]] about the discovery in 1970 of retroviral reverse transcriptase and its impact on life sciences research.

{{Viral proteins}}
{{Kinases}}
{{Authority control}}

[[Category:EC 2.7.7]]
[[Category:Molecular biology]]
[[Category:Viral enzymes]]
[[Category:Telomeres]]
[[Category:1970 in biology]]
[[Category:RNA reverse-transcribing viruses]]