Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F.

Rozen, Florence; Edery, Isaac; Meerovitch, Karen; Dever, Thomas E.; Merrick, William C.; Sonenberg, Nahum

doi:10.1128/mcb.10.3.1134

Cited by 581 publications

(455 citation statements)

References 68 publications

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“…However, an appreciable fraction of eIF4A is not bound in eIF4F 77 . eIF4A also associates with the initiation factors eIF4B and eIF4H, which are closely related RNA-binding proteins that enhance eIF4A association with RNA 84 and thereby increase the ability of eIF4A to unwind RNA and hydrolyse ATP in an RNA-stimulated fashion 85,86,87 . Together, these factors all promote formation of a translation initiation complex that allows binding of the small 40S ribosomal unit and other initiation factors to mRNA 88 .…”

Section: Nuclear Specklesmentioning

confidence: 99%

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

983

1,069

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Nearly all aspects of RNA metabolism, from transcription and translation to mRNA decay, involve RNA helicases, which are enzymes that use ATP to bind or remodel RNA and RNA-protein complexes (ribonucleoprotein (RNP) complexes) 1 . RNA helicases are found in all three domains of life, and many viruses also encode one or more of these proteins 2,3 . Together with the structurally related DNA helicases that function in replication, recombination and repair, the RNA helicases are classified into superfamilies and families, based on sequence and structural features 3,4 . DEAD box proteins form the largest helicase family, with 37 members in humans and 26 in Saccharomyces cerevisiae 3 , and are characterized by the presence of an Asp-Glu-Ala-Asp (DEAD) motif.DEAD box helicases have central and, in many cases, essential physiological roles in cellular RNA metabolism 5 (FIG. 1). The proteins generally function as part of larger multicomponent assemblies, such as the spliceosom e or the eukaryotic translation initiation machinery 6 . Mutations and deregulation of several DEAD box proteins have been linked to disease states, including cancer 7 . Although all DEAD box proteins contain a structurally highly conserved core with conserved ATP-binding and RNA-binding sites, different proteins have been associated with diverse and seemingly unrelated functions, including the disassembly of RNPs, chaperoning during RNA folding and even stabil ization of protein complexes on RNA 5,6 . How these highly conserved proteins fulfil such an array of different functions has been a long-standing question.Research has now started to illuminate the molecular basis for this functional diversity. In this Review, we summarize how structural data, together with biochemical and biophysical studies, have revealed unexpected modes by which these proteins function. We also discuss how novel molecular and cell biological approaches have better defined the cellular roles of DEAD box helicases. We outline our current view on common structural and mechan istic themes that have emerged, and on physical models of how these 'unusual' RNA helicases work.Structures of DEAD box RNA helicases A number of structural studies have universally shown that members of the DEAD box family contain a highly conserved helicase core that harbours the binding sites for ATP and RNA 3,4,8 . The core is surrounded by variable auxiliary domains, which are thought to be critical for the diverse functions of these enzymes.Structure of the helicase core. DEAD box proteins belong to helicase superfamily 2 (SF2) 2 . Similarly to all SF2 helicases, DEAD box proteins are built around a highly conserved helicase core of two virtually identical domains that resemble the bacterial recombination protein recombinase A (RecA) 3,4,8 (FIG. 2a,b). Within this helicase core, at least 12 characteristic sequence motifs are located at conserved positions (FIG. 2a,b). Some of these motifs are conserved across the entire SF2 family, whereas others are found only in the DEAD box family 3 ....

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Section: Nuclear Specklesmentioning

confidence: 99%

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

983

1,069

View full text Add to dashboard Cite

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“…Intriguingly, the DEAD box helicases comprise a family of proteins that catalyze unwinding of RNA. Members of this family include proteins involved in both translation initiation (eIF4A) and ribosomal RNA processing (Pause et al, 1994;Rozen et al, 1990). Although the biochemical function of this Myc target is currently unknown, its homologue in Drosophila has been named pitchoune as a consequence of the small size phenotype which results from its loss (Za ran et al, 1998).…”

Section: C-myc Target Genes and Growth Controlmentioning

confidence: 99%

The role of c-myc in cellular growth control

1999

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“…polypeptide has been difficult because translation factors mostly function as heteromericcomplexes. It has been shown that eIF-4A is an RNA helicase (Rozen et al, 1990;Pause & Sonenberg, 1992), eIF-4B, which contains the conserved eukaryotic RNAbinding domain, is an mRNA-binding protein (Naranda et al, 1994), and EF-la and EF-2 are GTPases (Lauer et al, 1984). eIF-5 also has been shown to possess GTPase activity (Trachsel & Staehelin, 1978;Brown-Luedi et al, 1982), even though the sequence of this protein does not contain the classical GTPbinding motifs Chakravarti & Maitra, 1993; E.V.…”

mentioning

confidence: 99%

Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF‐2B subunits revealed by analysis of conserved sequence motifs

Koonin

1995

Protein Science

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Computer-assisted analysis of amino acid sequences using methods for database screening with individual sequences and with multiple alignment blocks reveals a complex multidomain organization of yeast proteins CCD6 and CCD1 , and mammalian homolog of CCD6 -subunits of the eukaryotic translation initiation factor eIF-2B involved in GDP/GTP exchange on eIF-2. It is shown that these proteins contain a putative nucleotide-binding domain related to a variety of nucleotidyltransferases, most of which are involved in nucleoside diphosphate-sugar formation in bacteria. Three conserved motifs, one of which appears to be a variant of the phosphate-binding site (P-loop) and another that may be considered a specific version of the Mg2+-binding site of NTP-utilizing enzymes, were identified in the nucleotidyltransferase-related domain. Together with the third unique motif adjacent to the P-loop, these motifs comprise the signature of a new superfamily of nucleotide-binding domains. A domain consisting of hexapeptide amino acid repeats with a periodic distribution of bulky hydrophobic residues (isoleucine patch), which previously have been identified in bacterial acetyltransferases, is located toward the C-terminus from the nucleotidyltransferase-related domain. Finally, at the very C-termini of GCD6, ~I F -~B E , and two other eukaryotic translation initiation factors, eIF-4-y and eIF-5, there is a previously undetected, conserved domain. It is hypothesized that the nucleotidyltransferase-related domain is directly involved in the GDPIGTP exchange, whereas the C-terminal conserved domain may be involved in the interaction of eIF-2B, eIF-47, and eIF-5 with eIF-2.

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Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F.

Cited by 581 publications

References 68 publications

From unwinding to clamping — the DEAD box RNA helicase family

From unwinding to clamping — the DEAD box RNA helicase family

The role of c-myc in cellular growth control

Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF‐2B subunits revealed by analysis of conserved sequence motifs

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