Upstream open reading frame

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.

[1] 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.

[2] 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.

[3] 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_Pagliarini_Mootha_pp._7507–7512-4] 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.

[5] 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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