PUBLICATION

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

Authors
Chew, G.L., Pauli, A., Schier, A.F.
ID
ZDB-PUB-160525-9
Date
2016
Source
Nature communications   7: 11663 (Journal)
Registered Authors
Pauli, Andrea, Schier, Alexander
Keywords
Biological sciences, Bioinformatics, Evolution, Genetics
MeSH Terms
  • Protein Biosynthesis/genetics*
  • Mice
  • Zebrafish
  • Sequence Analysis, RNA
  • Regulatory Sequences, Ribonucleic Acid/genetics*
  • Models, Biological
  • RNA, Messenger/genetics*
  • Linear Models
  • 5' Untranslated Regions/genetics
  • Humans
  • Open Reading Frames/genetics*
  • Ribosomes/genetics
  • Ribosomes/metabolism
  • Conserved Sequence/genetics*
  • Animals
  • Molecular Sequence Annotation
  • Amino Acid Sequence/genetics
PubMed
27216465 Full text @ Nat. Commun.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping