Active Disruption of an RNA-Protein Interaction by a DExH/D RNA Helicase

Jankowsky, Eckhard; Gross, Christian H.; Shuman, Stewart; Pyle, Anna Marie

doi:10.1126/science.291.5501.121

Cited by 282 publications

(210 citation statements)

References 18 publications

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“…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 . Although it is not known whether protein removal and duplex unwinding by DEAD box proteins rely on identical mechanisms, observations are consistent with a displacement mode that is not based on translocation of the DEAD box protein 50 .…”

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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956

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

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956

1,069

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“…On the other hand, this mutant did reverse the siRNA-mediated inhibition of 28 S, suggesting that its RNA helicase activity may not be as critical as its ATPase, RNA folding activity, and/or interaction with other nucleolar factors for the production of 28 S rRNA. The ATPase activity of RH-II/Gu␣ might be critical in the formation and reorganization of ribonucleoprotein complexes required for 28 S rRNA production similar to the relevance of ATPase activity in the disruption of U1A-RNA interaction by RNA helicase NPH-II (45). The enhanced RNA folding activity of SAT-M1 mutant might contribute to this reorganization.…”

Section: Fig 6 Overexpression Of Rh-ii/gu␤ Blocks Rrna Productionmentioning

confidence: 99%

Silencing of RNA Helicase II/Guα Inhibits Mammalian Ribosomal RNA Production

Henning

Jin

et al. 2003

Journal of Biological Chemistry

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“…DEAD-box RNA helicases unwind RNA:RNA and RNA:DNA duplexes (Pause and Sonenberg 1992;Huang and Liu 2002), disrupt RNA-protein interactions (Jankowsky et al 2001), and have been implicated in rRNA processing, transcription, pre-RNA splicing, and mRNA transport (Rocak and Linder 2004). For example, the helicase Sub2p, the yeast homolog of Hel25E, functions in splicing, plays a pivotal role in RNA export by facilitating transcript binding to the export receptor, and also interacts with the THO complex (Strasser et al 2002).…”

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confidence: 99%

The Drosophila P68 RNA helicase regulates transcriptional deactivation by promoting RNA release from chromatin

Spradling¹

2006

Genes Dev.

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Terminating a gene's activity requires that pre-existing transcripts be matured or destroyed and that the local chromatin structure be returned to an inactive configuration. Here we show that the Drosophila homolog of the mammalian P68 RNA helicase plays a novel role in RNA export and gene deactivation. p68 mutations phenotypically resemble mutations in small bristles (sbr), the Drosophila homolog of the human mRNA export factor NXF1. Full-length hsp70 mRNA accumulates in the nucleus near its sites of transcription following heat shock of p68 homozygotes, and hsp70 gene shutdown is delayed. Unstressed mutant larvae show similar defects in transcript accumulation and gene repression at diverse loci, and we find that p68 mutations are allelic to Lighten-up, a known suppressor of position effect variegation. Our observations reveal a strong connection between transcript clearance and gene repression. P68 may be needed to rapidly remove transcripts from a gene before its activity can be shut down and its chromatin reset to an inactive state.

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Active Disruption of an RNA-Protein Interaction by a DExH/D RNA Helicase

Cited by 282 publications

References 18 publications

From unwinding to clamping — the DEAD box RNA helicase family

From unwinding to clamping — the DEAD box RNA helicase family

Silencing of RNA Helicase II/Guα Inhibits Mammalian Ribosomal RNA Production

The Drosophila P68 RNA helicase regulates transcriptional deactivation by promoting RNA release from chromatin

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