Abstract:
:Eukaryotic translation initiation begins with ribosomal recruitment of aminoacylated initiator tRNA (Met-tRNA(Met)(i)) by eukaryotic initiation factor eIF2. In cooperation with eIF3, eIF1, and eIF1A, Met-tRNA(Met)(i)/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 eIF2alpha 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(Met)(i). 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(Met)(i) 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.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Skabkin MA,Skabkina OV,Dhote V,Komar AA,Hellen CU,Pestova TVdoi
10.1101/gad.1957510subject
Has Abstractpub_date
2010-08-15 00:00:00pages
1787-801issue
16eissn
0890-9369issn
1549-5477pii
24/16/1787journal_volume
24pub_type
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