Alternative Translation Initiation at a UUG Codon Gives Rise to Two Functional Variants of the Mitochondria! Protein Kgd4

JOURNAL OF MOLECULAR BIOLOGY

卷:431

Article

Heublein, Manfred¹  Ndi, Mama¹  Vazquez-Calvo, Carmela¹  Voegtle, F-Nora²  Ott, Martin¹ 

[1] Stockholm Univ, Ctr Biomembrane Res, Dept Biochem & Biophys, SE-10691 Stockholm, Sweden

[2] Univ Freiburg, Fac Med, ZBMZ, Inst Biochem & Mol Biol, D-79104 Freiburg, Germany

关键词: mitochondria;    translation;    alternative initiation;    protein import;    biogenesis;   

DOI  :  10.1016/j.jmb.2019.02.023

来源: Elsevier

【 摘 要 】

Kgd4 is a novel subunit of the mitochondria! a-ketoglutarate dehydrogenase complex (KGDH). In yeast, the protein is present in two forms of unknown origin, as there is only one open reading frame and no alternative splicing. Here, we show that the two forms of Kgd4 derive from one mRNA that is translated by employing two alternative start sites. The standard, annotated AUG codon gives rise to the short form of the protein, while an upstream UUG codon is utilized to generate the larger form. However, both forms can be efficiently imported into mitochondria and stably incorporate into KGDH to support its activity. Translation of the long variant depends on sequences directly upstream of the alternative initiation site, demonstrating that translation initiation and its efficiency are dictated by the sequence context surrounding a specific codon. In summary, the two forms of Kgd4 follow a very unusual biogenesis pathway, supporting the notion that translation initiation in yeast is more flexible than it is widely recognized. (C) 2019 The Authors. Published by Elsevier Ltd.

【 授权许可】

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