The DEAD-box Helicase eIF4A: Paradigm or the Odd One Out?

RNA Biol. 2013 Jan;10(1):19-32. doi: 10.4161/rna.21966. Epub 2012 Sep 20.

Abstract

DEAD-box helicases catalyze the ATP-dependent unwinding of RNA duplexes. They share a helicase core formed by two RecA-like domains that carries a set of conserved motifs contributing to ATP binding and hydrolysis, RNA binding and duplex unwinding. The translation initiation factor eIF4A is the founding member of the DEAD-box protein family, and one of the few examples of DEAD-box proteins that consist of a helicase core only. It is an RNA-stimulated ATPase and a non-processive helicase that unwinds short RNA duplexes. In the catalytic cycle, a series of conformational changes couples the nucleotide cycle to RNA unwinding. eIF4A has been considered a paradigm for DEAD-box proteins, and studies of its function have revealed the governing principles underlying the DEAD-box helicase mechanism. However, as an isolated helicase core, eIF4A is rather the exception, not the rule. Most helicase modules in other DEAD-box proteins are modified, some by insertions into the RecA-like domains, and the majority by N- and C-terminal appendages. While the basic catalytic function resides within the helicase core, its modulation by insertions, additional domains or a network of interaction partners generates the diversity of DEAD-box protein functions in the cell. This review summarizes the current knowledge on eIF4A and its regulation, and discusses to what extent eIF4A serves as a model DEAD-box protein.

Keywords: ATP-driven conformational changes; DEAD-box helicase; RNA unwinding; translation initiation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / metabolism*
  • Eukaryotic Initiation Factor-4A / chemistry
  • Eukaryotic Initiation Factor-4A / metabolism*
  • Protein Binding
  • RNA / metabolism

Substances

  • RNA
  • Eukaryotic Initiation Factor-4A
  • DEAD-box RNA Helicases