The DEAD-Box Protein Dbp5 Controls mRNA Export by Triggering Specific RNA:Protein Remodeling Events

Tran, Elizabeth; Zhou, Yingna; Corbett, Anita H.; Wente, Susan R.

doi:10.1016/j.molcel.2007.09.019

Cited by 206 publications

(291 citation statements)

References 52 publications

(79 reference statements)

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“…Moreover, proteins can be displaced from structured and from unstructured RNA, suggesting that duplex unwinding is not required for release 49 . In accordance with a non-processive activit y of DEAD box proteins, protein displacement has been directly observed for proteins with a footprint of fewer than eight nucleotides [49][50][51][52] . Proteins with larger footprints cannot be displaced by DEAD box proteins, whereas other helicases readily remove such proteins 49,53 .…”

Section: Atp Ground Statementioning

confidence: 92%

“…In addition to ATPdependent RNA unwinding and clamping, DEAD box proteins can remove proteins from RNA in an ATPdriven reaction, as has been suggested for the removal of yeast Mud2 by the DEAD box protein Sub2 during pre-mRNA splicing and for the removal of mRNA export factor 67 (Mex67) during mRNA export by DEAD box protein 5 (Dbp5) [47][48][49][50][51][52] . Moreover, proteins can be displaced from structured and from unstructured RNA, suggesting that duplex unwinding is not required for release 49 .…”

Section: Atp Ground Statementioning

confidence: 99%

“…Genetic analyses suggest that Dbp5 affects the release of the mRNA export factor Mex67 from RNA, which is a critical step for mRNA export 48 . In addition, Dbp5 has been implicated in the release of nuclear polyadenylated RNA-binding 2 (Nab2) from mRNA 51 . How exactly Dbp5 affects the release of these two proteins is not clear.…”

Section: Nuclear Specklesmentioning

confidence: 99%

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From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

918

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: 92%

Section: Atp Ground Statementioning

confidence: 99%

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From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

918

1,069

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“…Inositol hexakisphosphate (IP 6 )-bound Gle1 activates DEAD box protein 5 (Dbp5; DDX19 in humans) on the cyptoplasmic face of the nuclear pore complex (NPC) (Alcazar-Roman et al, 2006) by stimulating ATP binding to Dbp5 . In return, Dbp5 mediates the dissociation of protein components from mRNPs (Tran et al, 2007. It has been reported that Gle1 has other functionally distinct roles in translation.…”

Section: Introductionmentioning

confidence: 99%

Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo

et al. 2016

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-GLE1 mutations cause lethal congenital contracture syndrome 1 (LCCS1), a severe autosomal recessive fetal motor neuron disease, and more recently have been associated with amyotrophic lateral sclerosis (ALS). The gene encodes a highly conserved protein with an essential role in mRNA export. The mechanism linking Gle1 function to motor neuron degeneration in humans has not been elucidated, but increasing evidence implicates abnormal RNA processing as a key event in the pathogenesis of several motor neuron

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“…When the pools of mRNAs immuneprecipitated by Npl3, Nab2, and Nab4 were determined in microarrays and compared, it was suggested that distinct sets of mRNAs are bound to each of these proteins (13). In vitro, the RNA helicase Dbp5 was shown to dissociate Nab2 from the mRNP 3 (14) and because of its localization on the cytoplasmic side of the nuclear pore complex, it was suggested that Dbp5 could release Nab2 from mRNPs after the nuclear exit. In addition, the binding of the import receptor Kap104 to Nab2 after export of the Nab2-containing mRNP into the cytoplasm was suggested to trigger release of Nab2 from the mRNA cargo (15).…”

mentioning

confidence: 99%

Purification of Nuclear Poly(A)-binding Protein Nab2 Reveals Association with the Yeast Transcriptome and a Messenger Ribonucleoprotein Core Structure

Batisse

Budd

et al. 2009

Journal of Biological Chemistry

101

107

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Nascent mRNAs produced by transcription in the nucleus are subsequently processed and packaged into mRNA ribonucleoprotein particles (messenger ribonucleoproteins (mRNPs)) before export to the cytoplasm. Here, we have used the poly(A)-binding protein Nab2 to isolate mRNPs from yeast under conditions that preserve mRNA integrity. Upon Nab2-tandem affinity purification, several mRNA export factors were co-enriched (Yra1, Mex67, THO-TREX) that were present in mRNPs of different size and mRNA length. High-throughput sequencing of the co-precipitated RNAs indicated that Nab2 is associated with the bulk of yeast transcripts with no specificity for different mRNA classes. Electron microscopy revealed that many of the mRNPs have a characteristic elongated structure. Our data suggest that mRNPs, although associated with different mRNAs, have a unifying core structure.Nucleocytoplasmic transport occurs via nuclear pore complexes, which are embedded into the nuclear membrane. For nuclear mRNA export, a conserved export receptor, Mex67-Mtr2, in yeast (TAP-p15 or NXF1-NXT1 in metazoans) and a number of export adaptor proteins were identified (for review, see Refs. 1 and 2).The TREX (transcription export) complex belongs to these adaptors and is composed of transcription elongation (THO complex) and export factors (Sub2 and Yra1). These proteins are loaded co-transcriptionally onto the pre-mRNA in yeast (3, 4), before recruitment of Mex67-Mtr2 occurs via an interaction with Yra1. A different assembly (Sac3-Thp1-Cdc31-Sus1 or TREX-2) is thought to facilitate the repositioning of transcribed genes to nuclear pore complexes and, thus, also helps to integrate transcription and export steps (2). Another adapter RNAbinding protein, Npl3, is recruited co-transcriptionally to the mRNA (5) and can interact with Mex67 in the nucleus when dephosphorylated (6).Finally, Nab2 is a poly(A) ϩ RNA-binding protein that shuttles between nucleus and cytoplasm and is required for mRNA export (1). Nab2 is mainly localized in the nucleus (7,8) and interacts with the poly(A)-binding protein (Pab1) to affect poly(A) tail length (9). Moreover, Nab2 interacts with Mlp1, a nuclear pore complex-associated protein at the nuclear basket involved in mRNP quality control (10), with Gfd1 and Gle1, factors involved in mRNA export (11), and with the Sac3-Thp1 complex, which plays a role in coupling transcription with mRNA metabolism (12). When the pools of mRNAs immuneprecipitated by Npl3, Nab2, and Nab4 were determined in microarrays and compared, it was suggested that distinct sets of mRNAs are bound to each of these proteins (13). In vitro, the RNA helicase Dbp5 was shown to dissociate Nab2 from the mRNP 3 (14) and because of its localization on the cytoplasmic side of the nuclear pore complex, it was suggested that Dbp5 could release Nab2 from mRNPs after the nuclear exit. In addition, the binding of the import receptor Kap104 to Nab2 after export of the Nab2-containing mRNP into the cytoplasm was suggested to trigger release of Nab2 from the mRNA cargo (15...

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The DEAD-Box Protein Dbp5 Controls mRNA Export by Triggering Specific RNA:Protein Remodeling Events

Cited by 206 publications

References 52 publications

From unwinding to clamping — the DEAD box RNA helicase family

From unwinding to clamping — the DEAD box RNA helicase family

Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo

Purification of Nuclear Poly(A)-binding Protein Nab2 Reveals Association with the Yeast Transcriptome and a Messenger Ribonucleoprotein Core Structure

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