RNA helicases at work: binding and rearranging

Jankowsky, Eckhard

doi:10.1016/j.tibs.2010.07.008

Cited by 475 publications

(498 citation statements)

References 104 publications

(176 reference statements)

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“…A range of biochemical activities Despite the high structural conservation of the helicase core, DEAD box proteins have been associated with an intriguing array of cellular functions, from disassembling RNPs to serving as immobile RNA clamps 1,25 . Similarly to most proteins involved in RNA metabolism, DEAD box proteins usually function within complexes containing dozens or even hundreds of components, such as the spliceosome or the nascent ribosome.…”

Section: Mitochondrial Rna Editingmentioning

confidence: 99%

“…RNA unwinding measured in vitro with defined model substrates is considered an excellent proxy for the ATP-dependent binding and remodelling of more complex RNA and RNP structures that DEAD box proteins are thought to perform in the cell during processes such as ribosome biogenesis or pre-mRNA splicing 1,26 . DEAD box proteins are bona fide heli cases that use ATP to bind and unwind RNA duplexes 27 .…”

Section: Mitochondrial Rna Editingmentioning

confidence: 99%

“…Unwinding efficiency also decreases with increasing duplex stability 28,29 . Singlestranded extensions to duplexes, at either the 3′ or 5′ end, stimulate unwindin g by many DEAD box proteins 1,6,30,31 but in a few instances extensions are not required -at least in vitro -for optima l activity 31 .…”

Section: Mitochondrial Rna Editingmentioning

confidence: 99%

“…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 .…”

Section: Introductionmentioning

confidence: 99%

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From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

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953

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: Mitochondrial Rna Editingmentioning

confidence: 99%

Section: Mitochondrial Rna Editingmentioning

confidence: 99%

Section: Mitochondrial Rna Editingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

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953

1,069

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“…DEAD-box proteins can be defined by the presence of 12 conserved motifs ( Jankowsky, 2011). Although individual motifs may vary as, for example, the DECD motif instead of DEAD in Sub2, the proteins are easily identified by the overall presence of these motifs.…”

Section: Introductionmentioning

confidence: 99%

DEAD-Box RNA Helicases in Gram-Positive RNA Decay

Redder

Linder

2012

Methods in Enzymology

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Biochemical characterization of Plasmodium falciparum parasite specific helicase 1 (PfPSH1)

et al. 2019

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Malaria, a disease caused by infection with parasites of the genus Plasmodium, causes millions of deaths worldwide annually. Of the five Plasmodium species that can infect humans, Plasmodium falciparum causes the most serious parasitic infection. The emergence of drug resistance and the ineffectiveness of old therapeutic regimes against malaria mean there is an urgent need to better understand the basic biology of the malaria parasite. Previously, we have reported the presence of parasite‐specific helicases identified through genome‐wide analysis of the P. falciparum (3D7) strain. Helicases are involved in various biological pathways in addition to nucleic acid metabolism, making them an important target of study. Here, we report the detailed biochemical characterization of P. falciparum parasite‐specific helicase 1 (PfPSH1) and the effect of phosphorylation on its biochemical activities. The C‐terminal of PfPSH1 (PfPSH1C) containing all conserved domains was used for biochemical characterization. PfPSH1C exhibits DNA‐ or ribonucleic acid (RNA)‐stimulated ATPase activity, and it can unwind DNA and RNA duplex substrates. It shows bipolar directionality because it can translocate in both (3′–5′ and 5′–3′) directions. PfPSH1 is mainly localized to the cytoplasm during early stages (including ring and trophozoite stages of intraerythrocytic development), but at late stages, it is partially located in the cytoplasm. The biochemical activities of PfPSH1 are upregulated after phosphorylation with PKC. The detailed biochemical characterization of PfPSH1 will help us understand its functional role in the parasite and pave the way for future studies.

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RNA helicases at work: binding and rearranging

Cited by 475 publications

References 104 publications

From unwinding to clamping — the DEAD box RNA helicase family

From unwinding to clamping — the DEAD box RNA helicase family

DEAD-Box RNA Helicases in Gram-Positive RNA Decay

Biochemical characterization of Plasmodium falciparum parasite specific helicase 1 (PfPSH1)

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