uORFs, reinitiation and alternative translation start sites in human mRNAs

Edited by Lev Kisselev

Received 17 February 2008; received in revised form 11 March 2008; accepted 12 March 2008. published online 20 March 2008.

Abstract

It is known that eukaryotic ribosomes are able to translate small ORFs and reinitiate translation at downstream start codons. However, this mechanism is widely considered to be inefficient and it is not commonly taken into account. We compiled a sample of human mRNAs containing small upstream ORFs overlapping with annotated protein coding sequences. Statistical analysis supported the hypothesis on reinitiation of translation at downstream AUG codons and functional significance of potential alternative ORFs. It may be assumed that some 5′UTR-located upstream ORFs can deliver ribosomes to alternative translation starts, and they should be taken into consideration in the prediction of human mRNA coding potential.

Keywords: Eukaryotic mRNA, Reinitiation, Upstream ORF, Protein isoforms, Translational control

a Institute of Cytology and Genetics, Lavrentieva Avenue 10, Novosibirsk 630090, Russia

b Novosibirsk State University, Novosibirsk 630090, Russia

c National Institute of Biomedical Innovation, 7-6-8, Saito Asagi, Ibaraki-shi, Osaka 567-0085, Japan

d Kyushu Institute of Technology, Iizuka 820-8502, Japan

Corresponding author. Address: Institute of Cytology and Genetics, Lavrentieva Avenue 10, Novosibirsk 630090, Russia. Fax: +7 383 3331278.

PII: S0014-5793(08)00243-3

doi:10.1016/j.febslet.2008.03.014

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