uAUG and uORFs in human and rodent 5'untranslated mRNAs.
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.
Iacono
Michele
M
Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano, Via Celoria, 26, 20133 Milano, Italy.
Mignone
Flavio
F
Pesole
Graziano
G
D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D003062:Codon; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D020121:5' Untranslated Regions; D003062:Codon; D012333:RNA, Messenger