title: Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish.
abstract: Upstream open reading frames (uORFs) are ubiquitous repressive genetic elements in vertebrate mRNAs. While much is known about the regulation of individual genes by their uORFs, the range of uORF-mediated translational repression in vertebrate genomes is largely unexplored. Moreover, it is unclear whether the repressive effects of uORFs are conserved across species. To address these questions, we analyse transcript sequences and ribosome profiling data from human, mouse and zebrafish. We find that uORFs are depleted near coding sequences (CDSes) and have initiation contexts that diminish their translation. Linear modelling reveals that sequence features at both uORFs and CDSes modulate the translation of CDSes. Moreover, the ratio of translation over 5' leaders and CDSes is conserved between human and mouse, and correlates with the number of uORFs. These observations suggest that the prevalence of vertebrate uORFs may be explained by their conserved role in repressing CDS translation.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Guo-Liang
authors.identifier: 0000-0003-4357-1404
authors.initials: GL
authors.lastname: Chew
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Andrea
authors.identifier: 0000-0001-9646-2303
authors.initials: A
authors.lastname: Pauli
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|The Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA.|FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.|Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D017124:Conserved Sequence / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D051379:Mice; D008954:Models, Biological; D058977:Molecular Sequence Annotation; D016366:Open Reading Frames / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D038621:Regulatory Sequences, Ribonucleic Acid / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015027:Zebrafish
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid