Generation of protein isoform diversity by alternative initiation of translation at non-AUG codons.
The use of several translation initiation codons in a single mRNA, by expressing several proteins from a single gene, contributes to the generation of protein diversity. A small, yet growing, number of mammalian mRNAs initiate translation from a non-AUG codon, in addition to initiating at a downstream in-frame AUG codon. Translation initiation on such mRNAs results in the synthesis of proteins harbouring different amino terminal domains potentially conferring on these isoforms distinct functions. Use of non-AUG codons appears to be governed by several features, including the sequence context and the secondary structure surrounding the codon. Selection of the downstream initiation codon can occur by leaky scanning of the 43S ribosomal subunit, internal entry of ribosome or ribosomal shunting. The biological significance of non-AUG alternative initiation is demonstrated by the different subcellular localisations and/or distinct biological functions of the isoforms translated from the single mRNA as illustrated by the two main angiogenic factor genes encoding the fibroblast growth factor 2 (FGF2) and the vascular endothelial growth factor (VEGF). Consequently, the regulation of alternative initiation of translation might have a crucial role for the biological function of the gene product.
Touriol
Christian
C
Institut National de la Santé et de la Recherche Médicale U589, Hormones, Facteurs de Croissance et Physiopathologie Vasculaire, Institut Fédératif de Recherche Louis Bugnard, C.H.U. Rangueil, 31403 Toulouse cedex 04, France.
Bornes
Stéphanie
S
Bonnal
Sophie
S
Audigier
Sylvie
S
Prats
Hervé
H
Prats
Anne-Catherine
AC
Vagner
Stéphan
S
D000818:Animals; D002451:Cell Compartmentation / Q000235:genetics; D018387:Codon, Initiator / Q000235:genetics*; D039642:Eukaryotic Initiation Factors / Q000235:genetics*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D014176:Protein Biosynthesis / Q000235:genetics*; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D018387:Codon, Initiator; D039642:Eukaryotic Initiation Factors; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2