uAUG and uORFs in human and rodent 5'untranslated mRNAs

Gene. 2005 Apr 11;349:97-105. doi: 10.1016/j.gene.2004.11.041.

Abstract

The control of translation is a fundamental mechanism in the regulation of gene expression. Among the cis-acting elements that play a role in translation regulation are upstream open reading frames (uORFs) and upstream AUG (uAUGs) located in the 5'UTR of mRNAs. We present here a genome-wide analysis of uAUGs and uORFs in a curated set of human and rodent mRNAs. Our study shows that the occurrence of uAUGs is suppressed more strongly than that of uORFs and that in-frame uAUGs are more strongly suppressed than out-of-frame uAUGs. A very similar pattern of uAUG/uORF frequency was also observed in mouse mRNAs. The analysis of orthologous 5'UTR sequences revealed a remarkable degree of evolutionary conservation only of those uORFs which acquired some functional activity. Our data suggest that besides leaky scanning and reinitiation, which likely occur with variable and gene-specific efficiency, the ribosome-shunt mechanism, eventually coupled to reinitiation after uORF translation, may be a widespread mode of translation regulation in eukaryotes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions*
  • Animals
  • Base Sequence
  • Codon
  • Conserved Sequence
  • Evolution, Molecular
  • Gene Expression Regulation
  • Humans
  • Mice
  • Molecular Sequence Data
  • Open Reading Frames*
  • Protein Processing, Post-Translational
  • RNA, Messenger / genetics
  • Rats

Substances

  • 5' Untranslated Regions
  • Codon
  • RNA, Messenger