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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.[1][2] 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.[3] 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.
Approximately 50% of human genes contain uORFs in their 5'UTR, and when present, these cause reductions in protein expression.[4] Human peptides derived from translated uORFs can be detected from cellular material with a mass spectrometer.[5]
^Vilela C, McCarthy JE (August 2003). "Regulation of fungal gene expression via short open reading frames in the mRNA 5'untranslated region". Molecular Microbiology. 49 (4): 859–67. doi:10.1046/j.1365-2958.2003.03622.x. PMID 12890013.
^Lovett PS, Rogers EJ (June 1996). "Ribosome regulation by the nascent peptide". Microbiological Reviews. 60 (2): 366–85. doi:10.1128/MMBR.60.2.366-385.1996. PMC 239448. PMID 8801438.
^Hinnebusch, Alan G. (1997-08-29). "Translational Regulation of Yeast GCN4: A window on factors that control initiator-tRNA binding to the ribosome *". Journal of Biological Chemistry. 272 (35): 21661–21664. doi:10.1074/jbc.272.35.21661. ISSN 0021-9258. PMID 9268289.
^Calvo SE, Pagliarini DJ, Mootha VK (May 2009). "Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 106 (18): 7507–12. Bibcode:2009PNAS..106.7507C. doi:10.1073/pnas.0810916106. PMC 2669787. PMID 19372376. Archived from the original on Dec 3, 2023 – via MIT Libraries.
^Slavoff SA, Mitchell AJ, Schwaid AG, Cabili MN, Ma J, Levin JZ, Karger AD, Budnik BA, Rinn JL, Saghatelian A (January 2013). "Peptidomic discovery of short open reading frame-encoded peptides in human cells". Nature Chemical Biology. 9 (1): 59–64. doi:10.1038/nchembio.1120. PMC 3625679. PMID 23160002.
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genomic location. For example, the translated product of an upstreamopenreadingframe (uORF) might be called a uORF-encoded peptide (uPEP). Micropeptides...
Tuija; Willis, Anne E. (2013). "A perspective on mammalian upstreamopenreadingframe function". The International Journal of Biochemistry & Cell Biology...
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characterizing the "Translational Effects and Coding Potential of an UpstreamOpenReadingFrame Associated with DOPA Responsive Dystonia (DRD)". Her research...
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fungus) controls alternative splicing to conditionally produce an UpstreamOpenReadingFrame (uORF), thereby affecting the expression of downstream genes...
Ambrosch I, Elbling L, Micksche M, Berger W (Apr 2001). "A small upstreamopenreadingframe causes inhibition of human major vault protein expression from...
mitochondrial ribosomal protein S29 (MRPS29) expression by a 5'-upstreamopenreadingframe". Mitochondrion. 10 (3): 274–83. doi:10.1016/j.mito.2009.12.150...
scanning the mRNA from 5' have TC bound and translate the first upstreamopenreadingframe (uORF). Under non-starving condition there is enough ternary...
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on upstreamopenreading frames located in the 5'UTR. The location of the second uORF, aptly named uORF2, overlaps with the ATF4 open-readingframe. During...
located on the short arm of chromosome 16 in humans, in the thirteenth openreadingframe. There are five transcript variants of this gene, named 1, 2, 3, 4...
total translation rate and Cln3 translation rate caused by an Upstreamopenreadingframe; another suggests that the increase in Cln3 activity at the end...
alpha-ketoacid dehydrogenase kinase mRNA is dependent upon an upstreamopenreadingframe in the 5'-untranslated region". The Journal of Biological Chemistry...
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imperfect hairpin that is immediately upstream of the predicted ribosome binding site (RBS) of the adjacent openreadingframe (ORF) suggesting a possible cis-regulatory...
c7orf26 (Chromosome 7, OpenReadingFrame 26) is a gene in humans that encodes a protein known as c7orf26 (uncharacterized protein c7orf26). Based on properties...
Uncharacterized protein Chromosome 16 OpenReadingFrame 71 is a protein in humans, encoded by the C16orf71 gene. The gene is expressed in epithelial tissue...
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variant was classified The 5 kb upstream/downstream readingframe provides for a more thorough analysis of upstream/downstream regions (the 1kb in ANNOVAR...
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