DEAD-box proteins: the driving forces behind RNA metabolism

Rocak, Sanda; Linder, Patrick

doi:10.1038/nrm1335

Cited by 709 publications

(706 citation statements)

References 98 publications

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“…The domain distribution of this catalogue ( Figure 1B) illustrates the presence of various known and well-studied RNA binding domains like RRM (RNA recognition motif) [30], K-homology (KH) [31,32], DEAD/DEAH box [33], dsrm [34], WD40 [35] in addition to unclassified domains like the Pkinase domain of EIF2AK2 that auto phosphorylates upon binding of RNA to the dsRBD domain of EIF2AK2 [36,37]. Also notable is the Calponin homology (CH) domain found in both cytoskeletal and signalling proteins [38].…”

Section: Resultsmentioning

confidence: 99%

The human RBPome: From genes and proteins to human disease

Neelamraju

Hashemikhabir

Janga

2015

Journal of Proteomics

114

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Section: Resultsmentioning

confidence: 99%

The human RBPome: From genes and proteins to human disease

Neelamraju

Hashemikhabir

Janga

2015

Journal of Proteomics

114

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“…DDX3 is characterized by a core segment of several spaced DEAD-box family conserved functional motifs (Rocak and Linder, 2004). As shown in Figure 5a, although the conserved core segment (DDX3 227-535 ) did not interact with eIF4E (lane 4), the N-terminal region (DDX3 1-226 ) showed a positive interaction (lane 3).…”

Section: Ddx3 Is An Eif4e-binding Proteinmentioning

confidence: 95%

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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“…13 In many DExH/ D-box proteins, the core helicase region is linked to different N-and/or C-terminal domains, and in some cases, these appended domains have been shown to target the proteins to their sites of action via protein-protein or protein-RNA interactions. [11][12][13] In N. crassa, the efficient splicing of a subset of mt group I introns requires both the mt tyrosyltRNA synthetase (mt TyrRS; CYT-18 protein), which stabilizes the catalytically active RNA structure, 14,15 and the DEAD-box protein CYT-19, which functions to resolve kinetic traps. 9 The requirement for CYT-19 in group I intron splicing was demonstrated both genetically and biochemically.…”

Section: Introductionmentioning

confidence: 99%

Involvement of DEAD-box Proteins in Group I and Group II Intron Splicing. Biochemical Characterization of Mss116p, ATP Hydrolysis-dependent and -independent Mechanisms, and General RNA Chaperone Activity

Halls

Mohr

Campo

et al. 2007

Journal of Molecular Biology

154

242

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The RNA-catalyzed splicing of group I and group II introns is facilitated by proteins that stabilize the active RNA structure or act as RNA chaperones to disrupt stable inactive structures that are kinetic traps in RNA folding. In Neurospora crassa and Saccharomyces cerevisiae, the latter function is fulfilled by specific DEAD-box proteins, denoted CYT-19 and Mss116p, respectively. Previous studies showed that purified CYT-19 stimulates the in vitro splicing of structurally diverse group I and group II introns and uses the energy of ATP binding or hydrolysis to resolve kinetic traps. Here, we purified Mss116p and show that it has RNA-dependent ATPase activity, unwinds RNA duplexes in a non-polar fashion, and promotes ATP-independent strand-annealing. Further, we show that Mss116p binds RNA non-specifically and promotes in vitro splicing of both group I and group II intron RNAs, as well as RNA cleavage by the aI5γ-derived D135 ribozyme. However, Mss116p also has ATP-hydrolysis-independent effects on some of these reactions, which are not shared by CYT-19 and may reflect differences in its RNA-binding properties. We also show that a non-mitochondrial DEAD-box protein, yeast Ded1p, can function almost as efficiently as CYT-19 and Mss116p in splicing the yeast aI5γ group II intron and less efficiently in splicing the bI1 group II intron. Together, our results show that Mss116p, like CYT-19, can act broadly as an RNA chaperone to stimulate the splicing of diverse group I and group II introns and that Ded1p also has an RNA chaperone activity that can be assayed by its effect on splicing mitochondrial introns. Nevertheless, these DEAD-box protein RNA chaperones are not completely interchangeable and appear to function in somewhat different ways using biochemical activities that have likely been tuned by coevolution to function optimally on specific RNA substrates.

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DEAD-box proteins: the driving forces behind RNA metabolism

Cited by 709 publications

References 98 publications

The human RBPome: From genes and proteins to human disease

The human RBPome: From genes and proteins to human disease

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

Involvement of DEAD-box Proteins in Group I and Group II Intron Splicing. Biochemical Characterization of Mss116p, ATP Hydrolysis-dependent and -independent Mechanisms, and General RNA Chaperone Activity

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