Translocation and Unwinding Mechanisms of RNA and DNA Helicases

Pyle, Anna Marie

doi:10.1146/annurev.biophys.37.032807.125908

Cited by 450 publications

(573 citation statements)

References 75 publications

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“…In the Sen1 Hel ‐ADP structure, the two RecA domains are positioned side by side, separated by a cleft about 10 Å wide (Fig 2). In this open conformation, RecA2 is rotated about 30° from the position it acquires in the closed conformation that is typical of helicases in the active RNA‐ATP‐bound state (Linder & Lasko, 2006; Pyle, 2008). Two mutations shown to affect the function of Sen1 in vivo map to the RecA domains and are likely to cause partial unfolding of the protein due to unfavorable electrostatic clashes (G1747D, DeMarini et al , 1992 and E1597K, Steinmetz & Brow, 1996).…”

Section: Resultsmentioning

confidence: 99%

“…Helicases of this family also contain two SF1B‐specific subdomains (1B and 1C) that modulate RNA binding (Cheng et al , 2007; Clerici et al , 2009; Chakrabarti et al , 2011; Lim et al , 2012). SF1B helicases bind nucleic acids with the same polarity as all other RNA‐dependent ATPases, that is, with the 3′ end at RecA1 and the 5′ end at RecA2 (reviewed in Pyle, 2008; Ozgur et al , 2015). However, the directionality of duplex unwinding of the SF1B superfamily is opposite to that of processive SF2 helicases, which unwind duplexes in the 3′‐5′ direction (Büttner et al , 2007).…”

Section: Introductionmentioning

confidence: 99%

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Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

et al. 2017

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The superfamily 1B (SF1B) helicase Sen1 is an essential protein that plays a key role in the termination of non‐coding transcription in yeast. Here, we identified the ~90 kDa helicase core of Saccharomyces cerevisiae Sen1 as sufficient for transcription termination in vitro and determined the corresponding structure at 1.8 Å resolution. In addition to the catalytic and auxiliary subdomains characteristic of the SF1B family, Sen1 has a distinct and evolutionarily conserved structural feature that “braces” the helicase core. Comparative structural analyses indicate that the “brace” is essential in shaping a favorable conformation for RNA binding and unwinding. We also show that subdomain 1C (the “prong”) is an essential element for 5′‐3′ unwinding and for Sen1‐mediated transcription termination in vitro. Finally, yeast Sen1 mutant proteins mimicking the disease forms of the human orthologue, senataxin, show lower capacity of RNA unwinding and impairment of transcription termination in vitro. The combined biochemical and structural data thus provide a molecular model for the specificity of Sen1 in transcription termination and more generally for the unwinding mechanism of 5′‐3′ helicases.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

et al. 2017

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“…DEAD box proteins differ from other DNA and RNA helicases in that they show no strict unwinding polarity 32 . It has become clear that this is because DEAD box proteins do not unwind duplexes based on translocation on the RNA 1,6,28,30,31,33 .…”

Section: Mitochondrial Rna Editingmentioning

confidence: 99%

From unwinding to clamping — the DEAD box RNA helicase family

Linder

Jankowsky

2011

Nat Rev Mol Cell Biol

907

1,002

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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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“…Superfamily 1 is one of the largest classes of helicases with members that participate in virtually all steps in DNA or RNA metabolism [82][83][84][85]. SF1 includes three families (Rep/UrvD, Pif1/RecD, and Upf1 like) [86] and can be divided into groups based on the direction of translocation on ssDNA: 3 -5 for SF1A helicases and 5 -3 for SF1B helicases [43].…”

Section: Superfamily 1 Helicasesmentioning

confidence: 99%

Erratum to: Structure and Mechanisms of SF1 DNA Helicases

Raney

Byrd

Aarattuthodiyil

2012

Advances in Experimental Medicine and Biology

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Superfamily I is a large and diverse group of monomeric and dimeric helicases defined by a set of conserved sequence motifs. Members of this class are involved in essential processes in both DNA and RNA metabolism in all organisms. In addition to conserved amino acid sequences, they also share a common structure containing two RecA-like motifs involved in ATP binding and hydrolysis and nucleic acid binding and unwinding. Unwinding is facilitated by a "pin" structure which serves to split the incoming duplex. This activity has been measured using both ensemble and single-molecule conditions. SF1 helicase activity is modulated through interactions with other proteins.

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Translocation and Unwinding Mechanisms of RNA and DNA Helicases

Cited by 450 publications

References 75 publications

Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

Sen1 has unique structural features grafted on the architecture of the Upf1‐like helicase family

From unwinding to clamping — the DEAD box RNA helicase family

Erratum to: Structure and Mechanisms of SF1 DNA Helicases

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