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The role of alternative translation start sites in the generation of human protein diversity


According to the scanning model, 40S ribosomal subunits initiate translation at the first (5′ proximal) AUG codon they encounter. However, if the first AUG is in a suboptimal context, it may not be recognized, and translation can then initiate at downstream AUG(s). In this way, a single RNA can produce several variant products. Earlier experiments suggested that some of these additional protein variants might be functionally important. We have analysed human mRNAs that have AUG triplets in 5′ untranslated regions and mRNAs in which the annotated translational start codon is located in a suboptimal context. It was found that 3% of human mRNAs have the potential to encode N-terminally extended variants of the annotated proteins and 12% could code for N-truncated variants. The predicted subcellular localizations of these protein variants were compared: 31% of the N-extended proteins and 30% of the N-truncated proteins were predicted to localize to subcellular compartments that differed from those targeted by the annotated protein forms. These results suggest that additional AUGs may frequently be exploited for the synthesis of proteins that possess novel functional properties.

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This work was supported by the Kyushu Institute of Technology 75th Commemoration Fund, Program of the Russian Academy of Sciences (Dynamics of Plant, Animal, and Human Gene Pools), the Russian Foundation for Basic Research (Grant No. 05-04-48207) and an RFBR-JSPS grant. We also thank the Siberian Division of the Russian Academy of Sciences (Complex Integration Program, Grant No. 59), and the Ministry of Industry, Science and Technologies of the Russian Federation (grant No. 2275.2003.4) for support.

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Correspondence to Alex V. Kochetov.

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Communicated by C. Hollenberg

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Kochetov, A.V., Sarai, A., Rogozin, I.B. et al. The role of alternative translation start sites in the generation of human protein diversity. Mol Genet Genomics 273, 491–496 (2005).

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  • Human mRNAs
  • AUG context
  • Subcellular localization
  • Protein polymorphism