期刊
GENES & DEVELOPMENT
卷 24, 期 16, 页码 1787-1801出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1957510
关键词
Ligatin; MCT-1; translation initiation; ribosomal recycling; HCV; Sindbis virus
资金
- NIH [GM59660, GM80623, AI51340]
Eukaryotic translation initiation begins with ribosomal recruitment of aminoacylated initiator tRNA (Met-tRNA(i)(Met)) by eukaryotic initiation factor eIF2. In cooperation with eIF3, eIF1, and eIF1A, Met-tRNA(i)(Met)/eIF2/GTP binds to 40S subunits yielding 43S preinitiation complexes that attach to the 5'-terminal region of mRNAs and then scan to the initiation codon to form 48S initiation complexes with established codon-anticodon base-pairing. Stress-activated phosphorylation of eIF2 alpha reduces the level of active eIF2, globally inhibiting translation. However, translation of several viral mRNAs, including Sindbis virus (SV) 26S mRNA and mRNAs containing hepatitis C virus (HCV)-like IRESs, is wholly or partially resistant to inhibition by eIF2 phosphorylation, despite requiring Met-tRNA(i)(Met). Here we report the identification of related proteins that individually (Ligatin) or together (the oncogene MCT-1 and DENR, which are homologous to N-terminal and C-terminal regions of Ligatin, respectively) promote efficient eIF2-independent recruitment of Met-tRNA(i)(Met) to 40S/mRNA complexes, if attachment of 40S subunits to the mRNA places the initiation codon directly in the P site, as on HCV-like IRESs and, as we show here, SV 26S mRNA. In addition to their role in initiation, Ligatin and MCT-1/DENR can promote release of deacylated tRNA and mRNA from recycled 40S subunits after ABCE1-mediated dissociation of post-termination ribosomes.
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