The Protein Family of RNA Helicases

Abstract

RNA helicases represent a large family of proteins that have been detected in almost all biological systems where RNA plays a central role. They are ubiquitously distributed over a wide range of organisms and are involved in nuclear and mitochondrial splicing processes, RNA editing, rRNA processing, translation initiation, nuclear mRNA export, and mRNA degradation. RNA helicases are described as essential factors in cell development and differentiation, and some of them play a role in transcription and replication of viral single-stranded RNA genomes. Comparisons of the conserved sequences reveal a close relationship between them and suggest that these proteins might be derived from a common ancestor. Biochemical studies have revealed a strong dependence of the unwinding activity on ATP hydrolysis. Although RNA helicase activity has only been demonstrated for a few examples yet, it is generally believed that all members of the largest subgroups, the DEAD and DEAH box proteins, exhibit this activity.

BRCA1 gene in breast cancer

“…A functional role for the BRCA1: BACH1 interaction in DNA repair was suggested by the finding that a BACH1 mutant with defective catalytic function interfered with DSB repair in a manner that was dependent on its ability to bind BRCA1. The DEAH box family (of which Rad3 is a member) includes DNA and RNA helicases, which participate in DNA repair, meiotic recombination, and various aspects of RNA processing and editing (Luking et al, 1998). It is interesting to speculate whether BACH1 may participate in the transcription-coupled repair function of BRCA1.…”

Effects of oligonucleotide length and atomic composition on stimulation of the ATPase activity of translation initiation factor eIF4A

“…To initiate translation, the 40S ribosomal subunit typically must find the 59-most AUG initiator codon in the 59 untranslated region (UTR) of an mRNA+ The ribosomal subunit is thought to accomplish this by first binding to an mRNA near the 59 cap and then scanning 59 to 39 along the 59 UTR in search of the first AUG codon+ These processes may be slowed by limited access to the 59 UTR+ Eukaryotic initiation factor 4A (eIF4A) has been proposed to promote translation initiation by using the energy from ATP hydrolysis to facilitate the loading of the ribosomal subunit onto mRNA and the removal of structure within the 59 UTR (for reviews see Hershey, 1991;Merrick & Hershey, 1996)+ Determining the biochemical capabilities of eIF4A is a necessary step toward understanding its biological function and how it performs this function+ eIF4A is the archetypal member of the DEAD box protein family (Linder et al+, 1989;Schmid & Linder, 1992)+ These proteins and the closely related DExH box proteins are involved in essentially all cellular RNA processes including pre-mRNA splicing, RNA degradation, ribosome biogenesis, RNA transport, and RNA localization (Wassarman & Steitz, 1991;Schmid & Linder, 1992;Lüking et al+, 1998)+ eIF4A also shares sequence similarity with DNA helicases (Koonin, 1991;Gorbalenya & Koonin, 1993)+ These observations support an RNA unwinding function for eIF4A and other DEAD box proteins, although alternative functions, such as maintaining the fidelity of biological processes by kinetic proofreading, rearranging RNA-protein interactions, and translocating complexes along RNA, have been proposed (Burgess & Guthrie, 1993;Staley & Guthrie, 1998;Lorsch & Herschlag, 1998a)+ eIF4A has been the focus of significant biochemical characterization+ In vitro, eIF4A bidirectionally unwinds duplexes containing single-stranded RNA overhangs+ This unwinding activity requires ATP, and is enhanced by the presence of another initiation factor, eIF4B, or by inclusion of eIF4A within the eIF4F complex (eIF4A•eIF4E•eIF4G) (Ray et al+, 1985;Lawson et al+, 1989;Rozen et al+, 1990;Rogers et al+, 1999)+ Mutagenesis of motifs conserved among DEAD box proteins has helped to define the role of these motifs in this unwinding reaction, as well as in RNA and ATP binding, ATP hydrolysis, and translation initiation (Schmid & Linder, 1991;Pause & Sonenberg, 1992;Pause et al+, 1993Pause et al+, , 1994)+ The effect of RNA structure, other translation factors and ATP on RNA binding by eIF4A has been assayed using cross-linking and fluorescence techniques …”

Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene

“…RNA helicases function primarily in destabilizing and unwinding dsRNA using energy generated by ATP hydrolysis (Gorbalenya and Koonin, 1993;Luking et al, 1998). They belong to helicase superfamily II and are grouped into three subfamilies based on the structure of their ATPase B motifs.…”

“…They belong to helicase superfamily II and are grouped into three subfamilies based on the structure of their ATPase B motifs. The three currently recognized families include the DEAD, DEAH and DExH box containing helicases (Gorbalenya and Koonin, 1993;Luking et al, 1998;Jankowsky and Jankowsky, 2000). RNA helicases are involved in every step of RNA metabolism including transcription, translation, RNA editing, splicing and degradation (Luking et al, 1998;Jankowsky and Jankowsky, 2000).…”