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.

uAUG and uORFs in human and rodent 5'untranslated mRNAs / M. Iacono, F. Mignone, G. Pesole. - In: GENE. - ISSN 0378-1119. - 349(2005), pp. 97-105. [10.1016/j.gene.2004.11.041]

uAUG and uORFs in human and rodent 5'untranslated mRNAs

F. Mignone
Secondo
;
2005

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.
mRNA translation; Post-transcriptional regulation; Ribosome shunting; Scanning model
2005
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/17120
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