Yeast elF4B binds to the head of the 40S ribosomal subunit and promotes mRNA recruitment through its N-terminal and internal repeat domains

• Published in: RNA (Cambridge) Vol. 19; no. 2; pp. 191 - 207
• Main Authors: Walker, SE, Zhou, F, Mitchell, S F, Larson, V S, Valasek, L, Hinnebusch, A G, Lorsch, J R
• Format: Journal Article
• Language: English
• Published: 01.02.2013
• ISSN: 1355-8382

Eukaryotic translation initiation factor (elF)4B stimulates recruitment of mRNA to the 43S ribosomal pre-initiation complex (PIC). Yeast elF4B (yelF4B), shown previously to bind single-stranded (ss) RNA, consists of an N-terminal domain (NTD), predicted to be unstructured in solution; an RNA-recognition motif (RRM); an unusual domain comprised of seven imperfect repeats of 26 amino acids; and a C-terminal domain. Although the mechanism of yelF4B action has remained obscure, most models have suggested central roles for its RRM and ssRNA-binding activity. We have dissected the functions of yelF4B's domains and show that the RRM and its ssRNA-binding activity are dispensable in vitro and in vivo. Instead, our data indicate that the 7-repeats and NTD are the most critical domains, which mediate binding of yelF4B to the head of the 40S ribosomal subunit via interaction with Rps20. This interaction induces structural changes in the ribosome's mRNA entry channel that could facilitate mRNA loading. We also show that yelF4B strongly promotes productive interaction of elF4A with the 43S times mRNA PIC in a manner required for efficient mRNA recruitment.