Yeast RNA helicases of the DEAD‐box family involved in translation initiation

Linder, Patrick

doi:10.1016/s0248-4900(03)00032-7

Cited by 100 publications

(93 citation statements)

References 109 publications

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“…Another paradigm of DEAD box protein function is exemplified by eIF4A 76,77 . Despite high similarity to eIF4AIII 78 , eIF4A seems to be targeted by a wide range of factors that regulate translation initiation, a pivotal step in gene expression 10,76,79 . The translation initiation factor eIF4A is the proto typical DEAD box protein 77 .…”

Section: Atp Ground Statementioning

confidence: 99%

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

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988

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: Atp Ground Statementioning

confidence: 99%

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

Self Cite

988

1,069

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“…The exact reason for this discrepancy is unclear. However, apart from translation, both Ded1p and DDX3 have been linked to transcription, splicing, ribosome biogenesis and nuclear transport (reviewed by Linder, 2003). Thus, the lethality of the ded1 deletion mutant and the ability to rescue the phenotype may result from defects and complementation effects involving cellular functions other than translation.…”

Section: Ddx3 Interacts With Eif4e and Regulates Translation J-w Shihmentioning

confidence: 99%

“…Based on sequence homology, DDX3 and its homologues, including Ded1p in yeast and PL10 in mouse, are assigned to the Ded1p subfamily (reviewed by Linder, 2003). Ded1p is required for translation initiation as suggested by genetic and biochemical analysis (Chuang et al, 1997;de la Cruz et al, 1997).…”

mentioning

confidence: 99%

Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein

Shih¹,

Tsai²,

Chao³

et al. 2007

Oncogene

163

199

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DDX3 is a human RNA helicase with plethoric functions. Our previous studies have indicated that DDX3 is a transcriptional regulator and functions as a tumor suppressor. In this study, we use a bicistronic reporter to demonstrate that DDX3 specifically represses cap-dependent translation but enhances hepatitis C virus internal ribosome entry site-mediated translation in vivo in a helicase activity-independent manner. To elucidate how DDX3 modulates translation, we identified translation initiation factor eukaryotic initiation factor 4E (eIF4E) as a DDX3-binding partner. Interestingly, DDX3 utilizes a consensus eIF4E-binding sequence YIPPHLR to interact with the functionally important dorsal surface of eIF4E in a similar manner to other eIF4E-binding proteins. Furthermore, cap affinity chromatography analysis suggests that DDX3 traps eIF4E in a translationally inactive complex by blocking interaction with eIF4G. Point mutations within the consensus eIF4E-binding motif in DDX3 impair its ability to bind eIF4E and result in a loss of DDX3's regulatory effects on translation. All these features together indicate that DDX3 is a new member of the eIF4E inhibitory proteins involved in translation initiation regulation. Most importantly, this DDX3-mediated translation regulation also confers the tumor suppressor function on DDX3. Altogether, this study demonstrates regulatory roles and action mechanisms for DDX3 in translation, cell growth and likely viral replication.

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“…Many of the biological functions of various helicases are listed in Table 2.1. Helicases are implicated in processes ranging from replication to translation [8,[10][11][12][46][47][48][49] and also in ATPdependent chromatin remodeling [50,51]. Replicative helicases deal with the process of nucleic acid replication (initiation, elongation, and termination).…”

Section: Functions Of Helicasesmentioning

confidence: 99%

“…By doing so, helicases allow access to the genetic information locked in the duplex DNA. Helicases participate in various aspects of nucleic acid metabolism such as DNA replication, recombination, repair, transcription, translation, and splicing of RNA transcripts [3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Erratum to: Structure and Mechanisms of SF1 DNA Helicases

Raney

Byrd

Aarattuthodiyil

2012

Advances in Experimental Medicine and Biology

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Superfamily I is a large and diverse group of monomeric and dimeric helicases defined by a set of conserved sequence motifs. Members of this class are involved in essential processes in both DNA and RNA metabolism in all organisms. In addition to conserved amino acid sequences, they also share a common structure containing two RecA-like motifs involved in ATP binding and hydrolysis and nucleic acid binding and unwinding. Unwinding is facilitated by a "pin" structure which serves to split the incoming duplex. This activity has been measured using both ensemble and single-molecule conditions. SF1 helicase activity is modulated through interactions with other proteins.

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Yeast RNA helicases of the DEAD‐box family involved in translation initiation

Cited by 100 publications

References 109 publications

From unwinding to clamping — the DEAD box RNA helicase family

From unwinding to clamping — the DEAD box RNA helicase family

Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein

Erratum to: Structure and Mechanisms of SF1 DNA Helicases

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