Unknown

Dataset Information

0

Sequential eukaryotic translation initiation factor 5 (eIF5) binding to the charged disordered segments of eIF4G and eIF2? stabilizes the 48S preinitiation complex and promotes its shift to the initiation mode.


ABSTRACT: During translation initiation in Saccharomyces cerevisiae, an Arg- and Ser-rich segment (RS1 domain) of eukaryotic translation initiation factor 4G (eIF4G) and the Lys-rich segment (K-boxes) of eIF2? bind three common partners, eIF5, eIF1, and mRNA. Here, we report that both of these segments are involved in mRNA recruitment and AUG recognition by distinct mechanisms. First, the eIF4G-RS1 interaction with the eIF5 C-terminal domain (eIF5-CTD) directly links eIF4G to the preinitiation complex (PIC) and enhances mRNA binding. Second, eIF2?-K-boxes increase mRNA binding to the 40S subunit in vitro in a manner reversed by the eIF5-CTD. Third, mutations altering eIF4G-RS1, eIF2?-K-boxes, and eIF5-CTD restore the accuracy of start codon selection impaired by an eIF2? mutation in vivo, suggesting that the mutual interactions of the eIF segments within the PIC prime the ribosome for initiation in response to start codon selection. We propose that the rearrangement of interactions involving the eIF5-CTD promotes mRNA recruitment through mRNA binding by eIF4G and eIF2? and assists the start codon-induced release of eIF1, the major antagonist of establishing tRNA(i)(Met):mRNA binding to the P site.

SUBMITTER: Singh CR 

PROVIDER: S-EPMC3457530 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Sequential eukaryotic translation initiation factor 5 (eIF5) binding to the charged disordered segments of eIF4G and eIF2β stabilizes the 48S preinitiation complex and promotes its shift to the initiation mode.

Singh Chingakham Ranjit CR   Watanabe Ryosuke R   Chowdhury Wasimul W   Hiraishi Hiroyuki H   Murai Marcelo J MJ   Yamamoto Yasufumi Y   Miles David D   Ikeda Yuka Y   Asano Masayo M   Asano Katsura K  

Molecular and cellular biology 20120730 19


During translation initiation in Saccharomyces cerevisiae, an Arg- and Ser-rich segment (RS1 domain) of eukaryotic translation initiation factor 4G (eIF4G) and the Lys-rich segment (K-boxes) of eIF2β bind three common partners, eIF5, eIF1, and mRNA. Here, we report that both of these segments are involved in mRNA recruitment and AUG recognition by distinct mechanisms. First, the eIF4G-RS1 interaction with the eIF5 C-terminal domain (eIF5-CTD) directly links eIF4G to the preinitiation complex (PI  ...[more]

Similar Datasets

| S-EPMC4231746 | biostudies-literature
| S-EPMC1589998 | biostudies-literature
| S-EPMC3917153 | biostudies-literature
| S-EPMC85746 | biostudies-literature
| S-EPMC5062967 | biostudies-literature
| S-EPMC3172263 | biostudies-literature
| S-EPMC2875157 | biostudies-literature
| S-EPMC1367198 | biostudies-literature
| S-EPMC4150770 | biostudies-literature
| S-EPMC1421092 | biostudies-literature