Editing Open reading frame (section)

==Biological significance==
One common use of open reading frames (ORFs) is as one piece of evidence to assist in [[gene prediction]]. Long ORFs are often used, along with other evidence, to initially identify candidate [[Genetic code|protein-coding]] regions or [[Non-coding RNA|functional RNA]]-coding regions in a [[DNA]] sequence.<ref name=deonier2005p25 /> The presence of an ORF does not necessarily mean that the region is always [[Translation (genetics)|translated]]. For example, in a randomly generated DNA sequence with an equal percentage of each [[nucleotide]], a [[stop-codon]] would be expected once every 21 [[codon]]s.<ref name=deonier2005p25 /> A simple gene prediction algorithm for [[prokaryotes]] might look for a [[start codon]] followed by an open reading frame that is long enough to encode a typical protein, where the [[Codon usage bias|codon usage]] of that region matches the frequency characteristic for the given organism's coding regions.<ref name=deonier2005p25 /> Therefore, some authors say that an ORF should have a minimal length, e.g. 100 codons<ref name="Claverie_1997">{{cite journal | vauthors = Claverie JM, Poirot O, Lopez F | title = The difficulty of identifying genes in anonymous vertebrate sequences | journal = Computers & Chemistry | volume = 21 | issue = 4 | pages = 203–14 | date = 1997 | pmid = 9415985 | doi = 10.1016/s0097-8485(96)00039-3 }}</ref> or 150 codons.<ref name=deonier2005p25>{{cite book | vauthors = Deonier R, Tavaré S, Waterman M |title = Computational Genome Analysis: an introduction |publisher = [[Springer-Verlag]] |year = 2005 |isbn = 978-0-387-98785-9 |page=25|author2-link = Simon Tavaré }}</ref> By itself even a long open reading frame is not conclusive evidence for the presence of a [[gene]].<ref name=deonier2005p25 />

===Short open reading frames===
Some '''short open reading frames''',<ref>{{cite journal | pmid=35300685 | doi=10.1186/s12929-022-00802-5 | title=Short open reading frames (sORFs) and microproteins: an update on their identification and validation measures | year=2022 | journal=Journal of Biomedical Science| doi-access=free | last1=Leong | first1=Alyssa Zi-Xin | last2=Lee | first2=Pey Yee | last3=Mohtar | first3=M. Aiman | last4=Syafruddin | first4=Saiful Effendi | last5=Pung | first5=Yuh-Fen | last6=Low | first6=Teck Yew | volume=29 | issue=1 | page=19 | pmc=8928697 }}</ref> also named '''small open reading frames''',<ref>{{cite journal | pmid=36543139 | doi=10.1016/j.celrep.2022.111808 | title=De novo birth of functional microproteins in the human lineage | year=2022 | last1=Vakirlis | first1=Nikolaos | last2=Vance | first2=Zoe | last3=Duggan | first3=Kate M. | last4=McLysaght | first4=Aoife | journal=Cell Reports | volume=41 | issue=12 | page=111808 | pmc=10073203 | s2cid=254966620 }}</ref> abbreviated as '''sORFs''' or '''smORFs''', usually < 100 codons in length,<ref>{{cite journal | doi=10.3389/fgene.2021.796060 | doi-access=free | title=Small Open Reading Frames, How to Find Them and Determine Their Function | year=2022 | last1=Kute | first1=Preeti Madhav | last2=Soukarieh | first2=Omar | last3=Tjeldnes | first3=Håkon | last4=Trégouët | first4=David-Alexandre | last5=Valen | first5=Eivind | journal=Frontiers in Genetics | volume=12 | page=796060 | pmid=35154250 | pmc=8831751 }}</ref> that lack the classical hallmarks of protein-coding genes (both from ncRNAs and mRNAs) can produce functional [[peptide]]s.<ref name="ZanetBenrabah2015">{{cite journal | vauthors = Zanet J, Benrabah E, Li T, Pélissier-Monier A, Chanut-Delalande H, Ronsin B, Bellen HJ, Payre F, Plaza S | display-authors = 6 | title = Pri sORF peptides induce selective proteasome-mediated protein processing | journal = Science | volume = 349 | issue = 6254 | pages = 1356–1358 | date = September 2015 | pmid = 26383956 | doi = 10.1126/science.aac5677 | s2cid = 206639549 | bibcode = 2015Sci...349.1356Z | url = https://hal.inrae.fr/hal-04767052v1/file/zanet%202015.pdf }}</ref> They encode [[microprotein]]s or sORF‐encoded proteins (SEPs). The 5’-UTR of about 50% of mammal mRNAs are known to contain one or several sORFs,<ref>{{cite journal | vauthors = Wethmar K, Barbosa-Silva A, Andrade-Navarro MA, Leutz A | title = uORFdb--a comprehensive literature database on eukaryotic uORF biology | journal = Nucleic Acids Research | volume = 42 | issue = Database issue | pages = D60–D67 | date = January 2014 | pmid = 24163100 | pmc = 3964959 | doi = 10.1093/nar/gkt952 }}</ref> also called [[upstream ORF]]s or uORFs. However, less than 10% of the vertebrate mRNAs surveyed in an older study contained AUG codons in front of the major ORF. Interestingly, uORFs were found in two thirds of proto-oncogenes and related proteins.<ref>{{Cite journal|last1=Geballe|first1=A. P.|last2=Morris|first2=D. R.|date=April 1994|title=Initiation codons within 5'-leaders of mRNAs as regulators of translation|url=https://pubmed.ncbi.nlm.nih.gov/8016865|journal=Trends in Biochemical Sciences|volume=19|issue=4|pages=159–164|doi=10.1016/0968-0004(94)90277-1|issn=0968-0004|pmid=8016865}}</ref> 64–75% of experimentally found translation initiation sites of sORFs are conserved in the genomes of human and mouse and may indicate that these elements have function.<ref>{{cite journal | vauthors = Lee S, Liu B, Lee S, Huang SX, Shen B, Qian SB | title = Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 37 | pages = E2424–E2432 | date = September 2012 | pmid = 22927429 | pmc = 3443142 | doi = 10.1073/pnas.1207846109 | doi-access = free }}</ref> However, sORFs can often be found only in the minor forms of mRNAs and avoid selection; the high conservation of initiation sites may be connected with their location inside promoters of the relevant genes. This is characteristic of [[SLAMF1]] gene, for example.<ref>{{cite journal | vauthors = Schwartz AM, Putlyaeva LV, Covich M, Klepikova AV, Akulich KA, Vorontsov IE, Korneev KV, Dmitriev SE, Polanovsky OL, Sidorenko SP, Kulakovskiy IV, Kuprash DV | display-authors = 6 | title = Early B-cell factor 1 (EBF1) is critical for transcriptional control of SLAMF1 gene in human B cells | journal = Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms | volume = 1859 | issue = 10 | pages = 1259–1268 | date = October 2016 | pmid = 27424222 | doi = 10.1016/j.bbagrm.2016.07.004 }}</ref>