biostudies-literatureRocha ALNSFNIA NIH HHSNIMH NIH HHSNCI NIH HHSNINDS NIH HHSNIHNIGMS NIH HHSNIH HHS168559https://www.ebi.ac.uk/biostudies/studies/S-EPMC11292582biostudies-literatureUnknown436(10)Upstream open reading frames (uORFs) are cis-acting elements that can dynamically regulate the translation of downstream ORFs by suppressing downstream translation under basal conditions and, in some cases, increasing downstream translation under stress conditions. Computational and empirical methods have identified uORFs in the 5'-UTRs of approximately half of all mouse and human transcripts, making uORFs one of the largest regulatory elements known. Because the prevailing dogma was that eukaryotic mRNAs produce a single functional protein, the peptides and small proteins, or microproteins, encoded by uORFs were rarely studied. We hypothesized that a uORF in the SLC35A4 mRNA is producing a functional microprotein (SLC35A4-MP) because of its conserved amino acid sequence. Through a series Journal of molecular biologyAn Inner Mitochondrial Membrane Microprotein from the SLC35A4 Upstream ORF Regulates Cellular Metabolism.PMC11292582S10 OD021784R01 NS108934R01 GM138780RF1 MH129261P30 CA014195R01 AG065549R01 AG062479U24 NS120055R01 GM102491R01 AG081037Chu QEllisman MHRocha ALPerkins GDe Souza EVPai VChang TMa JDiedrich JKVaughan JMSaghatelian AfalseAn Inner Mitochondrial Membrane Microprotein from the SLC35A4 Upstream ORF Regulates Cellular Metabolism.Upstream open reading frames (uORFs) are cis-acting elements that can dynamically regulate the translation of downstream ORFs by suppressing downstream translation under basal conditions and, in some cases, increasing downstream translation under stress conditions. Computational and empirical methods have identified uORFs in the 5'-UTRs of approximately half of all mouse and human transcripts, making uORFs one of the largest regulatory elements known. Because the prevailing dogma was that eukaryotic mRNAs produce a single functional protein, the peptides and small proteins, or microproteins, encoded by uORFs were rarely studied. We hypothesized that a uORF in the SLC35A4 mRNA is producing a functional microprotein (SLC35A4-MP) because of its conserved amino acid sequence. Through a series 2024-01-01T00:00:00Z2024 May2025-04-27T02:03:02.772Z2025-04-06T18:28:34.002ZS-EPMC112925823858007710.1016/j.jmb.2024.168559