upstream open reading frame
{{Technical| date=October 2022}}
{{TOCright}}
An upstream open reading frame (uORF) is an open reading frame (ORF) within the 5' untranslated region (5'UTR) of an mRNA. uORFs can regulate eukaryotic gene expression.{{cite journal | vauthors = Vilela C, McCarthy JE | title = Regulation of fungal gene expression via short open reading frames in the mRNA 5'untranslated region | journal = Molecular Microbiology | volume = 49 | issue = 4 | pages = 859–67 | date = August 2003 | pmid = 12890013 | doi = 10.1046/j.1365-2958.2003.03622.x | doi-access = free }}{{cite journal | vauthors = Lovett PS, Rogers EJ | title = Ribosome regulation by the nascent peptide |doi-access=free | journal = Microbiological Reviews | volume = 60 | issue = 2 | pages = 366–85 | date = June 1996 | pmid = 8801438 | pmc = 239448 | doi = 10.1128/MMBR.60.2.366-385.1996}} Translation of the uORF typically inhibits downstream expression of the primary ORF. However, in some genes such as yeast GCN4, translation of specific uORFs may increase translation of the main ORF.{{Cite journal|last=Hinnebusch|first=Alan G.|date=1997-08-29|title=Translational Regulation of Yeast GCN4: A window on factors that control initiator-tRNA binding to the ribosome *|url=https://www.jbc.org/article/S0021-9258(19)65604-8/abstract|journal=Journal of Biological Chemistry|language=English|volume=272|issue=35|pages=21661–21664|doi=10.1074/jbc.272.35.21661|pmid=9268289|issn=0021-9258|doi-access=free}}
In humans
Approximately 50% of human genes contain uORFs in their 5'UTR, and when present, these cause reductions in protein expression.{{cite journal | vauthors = Calvo SE, Pagliarini DJ, Mootha VK | title = Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 18 | pages = 7507–12 | date = May 2009 | pmid = 19372376 | doi = 10.1073/pnas.0810916106 | via=MIT Libraries | url = http://dspace.mit.edu/bitstream/1721.1/50259/1/Calvo-2009-Upstream%20open%20readin.pdf |bibcode-access=free | pmc=2669787| bibcode = 2009PNAS..106.7507C | doi-access = free |url-status=live |archive-url=https://web.archive.org/web/20231203070445/https://dspace.mit.edu/bitstream/handle/1721.1/50259/Calvo-2009-Upstream%20open%20readin.pdf;jsessionid=FAF8DFA847117352F204BDD162D2E1B4?sequence=1 |archive-date= Dec 3, 2023 }} Human peptides derived from translated uORFs can be detected from cellular material with a mass spectrometer.{{cite journal | vauthors = Slavoff SA, Mitchell AJ, Schwaid AG, Cabili MN, Ma J, Levin JZ, Karger AD, Budnik BA, Rinn JL, Saghatelian A | title = Peptidomic discovery of short open reading frame-encoded peptides in human cells | journal = Nature Chemical Biology | volume = 9 | issue = 1 | pages = 59–64 | date = January 2013 | pmid = 23160002 | pmc = 3625679 | doi = 10.1038/nchembio.1120 }}
uORFs were found in two thirds of proto-oncogenes and related proteins.{{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}}
In bacteria
In bacteria, uORFs are called leader peptides and were originally discovered on the basis of their impact on the regulation of genes involved in the synthesis or transport of amino acids.
See also
References
{{Reflist}}
{{genetics-stub}}
{{DEFAULTSORT:Upstream open reading frame}}