Ddx42p--a human DEAD box protein with RNA chaperone activities

Uhlmann‐Schiffler, Heike; Jalal, Carolin; Stahl, Hans

doi:10.1093/nar/gkj403

Cited by 52 publications

(57 citation statements)

References 73 publications

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“…Ddx42p is related to Ddx5 and Ddx17 closer than any other known DEAD protein, yet differs in biochemical features (Uhlmann-Schiffler et al, 2006). It was found in the 17S U2 snRNP splicing complex .…”

Section: Introductionmentioning

confidence: 91%

The DEAD box protein Ddx42p modulates the function of ASPP2, a stimulator of apoptosis

2009

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Ddx42p is a recently characterized mammalian DEAD box protein with unknown cellular function. We found that in human cells Ddx42p physically interacts with ASPP2, a major apoptosis inducer known to enhance p53 transactivation of proapoptotic genes. The proteins interact via a domain within the carboxy-terminal part of Ddx42p and a mid-amino-terminal sequence as well as the ankyrin-SH3 region of ASPP2. Overexpression of Ddx42p interferes with apoptosis induction by ASPP2, whereas Ddx42p knockdown reduces the survival rate of cultured human cells. In addition, ASPP2 is found in cytoplasm and nucleus at low Ddx42p level, and predominantly in cytoplasm at high concentration of Ddx42p, respectively. Our results show that Ddx42p is capable of modulating ASPP2 function.

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Section: Introductionmentioning

confidence: 91%

The DEAD box protein Ddx42p modulates the function of ASPP2, a stimulator of apoptosis

2009

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“…Many helicases, including several DEAD box proteins, not only catalyse the unwinding of duplexes but also show strand annealing activity, at least in vitro 26,[54][55][56][57][58] . For example, nucleolar RNA helicase 2 (RH2; also known as Gu and DDX21) displays intrinsi c ATP-independent RNA folding activity, the intramolecular version of strand annealing 59 .…”

Section: Atp Ground Statementioning

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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“…The assay was performed with C2 and C 0 3 RNAs (0.5 nM each), C2 RNA alone (0.5 nM), or C 0 3 RNA alone (0.5 nM), the indicated concentration of NS3H (upper panels) or mNS3H (lower panels), 2.5 mM ATP, and 1.5 mM MnCl 2 at 37°C for 1 h. The reaction mixtures were treated with proteinase K before resolving by gel electrophoresis for detecting dsRNA formation (lanes 1-5). Alternatively, the reaction mixtures were directly resolved by gel electrophoresis for detecting RNA binding (lanes [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Notably, a large fraction of the RNA-protein complex did not migrate into the gel well at 100 nM and 400 nM NS3H or mNS3H.…”

Section: Dsrna and Ssrna Inter-conversionmentioning

confidence: 99%

HCV NS3 protein helicase domain assists RNA structure conversion

Huang

Wang

2010

FEBS Letters

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Edited by Hans-Dieter KlenkKeywords: HCV NS3 helicase RNA structure conversion Strand annealing dsRNA unwinding RNA chaperone DExH/D-box protein a b s t r a c t NS3H, the helicase domain of HCV NS3, possesses RNA-stimulated ATPase and ATP hydrolysis-dependent dsRNA unwinding activities. Here, the ability of NS3H to facilitate RNA structural rearrangement is studied using relatively long RNA strands as the model substrates. NS3H promotes intermolecular annealing, resolves three-stranded RNA duplexes, and assists dsRNA and ssRNA inter-conversions to establish a steady state among RNA structures. NS3H facilitates RNA structure conversions in a mode distinct from an ATP-independent RNA chaperone. These findings expand the known function of HCV NS3 helicase and reveal a role for viral helicase in assisting RNA structure conversions during virus life cycle.

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Ddx42p--a human DEAD box protein with RNA chaperone activities

Cited by 52 publications

References 73 publications

The DEAD box protein Ddx42p modulates the function of ASPP2, a stimulator of apoptosis

The DEAD box protein Ddx42p modulates the function of ASPP2, a stimulator of apoptosis

From unwinding to clamping — the DEAD box RNA helicase family

HCV NS3 protein helicase domain assists RNA structure conversion

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