Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish.

Nat Commun
Authors
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.

Year of Publication
2016
Journal
Nat Commun
Volume
7
Pages
11663
Date Published
2016 May 24
ISSN
2041-1723
URL
DOI
10.1038/ncomms11663
PubMed ID
27216465
PubMed Central ID
PMC4890304
Links
Grant list
K99 HD076935 / HD / NICHD NIH HHS / United States
R01 GM056211 / GM / NIGMS NIH HHS / United States
R01 HD076708 / HD / NICHD NIH HHS / United States