DENR-MCT-1 promotes translation re-initiation downstream of uORFs to control tissue growth

Article

关键词: MSL-2 MESSENGER-RNA;    OPEN READING FRAMES;    CANDIDATE ONCOGENE;    INSULIN-RECEPTOR;    GENE-EXPRESSION;    SEX-LETHAL;    DROSOPHILA;    MECHANISM;    PROTEIN;    MCT-1;   

DOI  :  10.1038/nature13401

来源: SCIE

【 摘 要 】

During cap-dependent eukaryotic translation initiation, ribosomes scan messenger RNA from the 5' end to the first AUG start codon with favourable sequence context(1,2). For many mRNAs this AUG belongs to a short upstream open reading frame (uORF)(3), and translation of the main downstream ORF requires re-initiation, an incompletely understood process(1,4-6). Re-initiation is thought to involve the same factors as standard initiation(1,5,7). It is unknown whether any factors specifically affect translation re-initiation without affecting standard cap-dependent translation. Here we uncover the non-canonical initiation factors density regulated protein (DENR) and multiple copies in T-cell lymphoma-1(MCT-1; also called MCTS1 inhumans) as the first selective regulators of eukaryotic re-initiation. mRNAs containing upstream ORFs with strong Kozak sequences selectively require DENR-MCT-1 for their proper translation, yielding a novel class of mRNAs that can be co-regulated and that is enriched for regulatory proteins such as oncogenic kinases. Collectively, our data reveal that cells have a previously unappreciated translational control system with a key role in supporting proliferation and tissue growth.

【 授权许可】

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