DEAD-box-protein-assisted RNA Structure Conversion Towards and Against Thermodynamic Equilibrium Values

Yang, Quansheng; Fairman, Margaret E.; Jankowsky, Eckhard

doi:10.1016/j.jmb.2007.02.071

Cited by 35 publications

(46 citation statements)

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“…A consequence of non-specific unfolding activity is that DExD/H-box proteins can drive folding away from thermodynamic equilibrium, and such effects have recently been demonstrated for Ded1p and CYT-19 [42,43,46]. These results suggest that, subsequent to each ATP-driven unfolding event, the RNA repartitions between folding forms based on the kinetics of this partitioning rather than the stability of the ultimate folded states.…”

Section: How Atp-dependent Rna Chaperones Assist Foldingmentioning

confidence: 95%

“…Furthermore, the ATP-driven unfolding activity actively redistributes the conformational ensemble of structured RNAs, populating intermediates that otherwise would be rare at thermodynamic equilibrium [46] -The authors investigate the activity of Ded1p, a DEAD-box protein, in a model system and observe its ability to populate less stable structures by converting more stable structures to misfolded ones using the energy from ATP hydrolysis.…”

Section: Reference Annotationsmentioning

confidence: 99%

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Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Chu

Herschlag

2008

Current Opinion in Structural Biology

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SummaryThe rapid development of our understanding of the diverse biological roles fulfilled by non-coding RNA has motivated interest in the basic macromolecular behavior, structure, and function of RNA. We focus on two areas in the behavior of complex RNAs. First, we present advances in the understanding of how RNA folding is accomplished in vivo by presenting a mechanism for the action of DEAD-box proteins. Members of this family are intimately associated with almost all cellular processes involving RNA, mediating RNA structural rearrangements and chaperoning their folding. Next, we focus on advances in understanding and characterizing the basic biophysical forces that govern the folding of complex RNAs. Ultimately we expect that a confluence and synergy between these approaches will lead to profound understanding of RNA and its biology.The explosion in our knowledge about noncoding RNA (ncRNA) -RNA that is not translated into protein -has expanded interest in RNA beyond the traditional RNA community. Diverse ncRNAs include the recently-discovered riboswitches, whose novel gene-regulation function is induced by the binding of small metabolites [1]; most of the so-called "Human Accelerated Regions" (HAR) of the human genome, whose recent evolution may be linked to the emergence of the human brain [2]; and many ncRNAs of unknown function [3]. These discoveries underscore the need to understand the fundamental macromolecular behavior of RNA, its structure and dynamics, and how these RNAs are handled and exploited in biology.Study of catalytic RNAs, which allow detection of correct folding via activity measurements, has established basic thermodynamic and kinetic properties of RNA folding. Large catalytic RNAs such as the group I intron from Tetrahymena thermophila and the RNase P RNA from Bacillus subtilis fold at vastly different rates under different conditions upon addition of Mg 2+ and have been shown to fold via multiple parallel pathways, in which different molecules follow different routes with different rates and intermediates, to a common final folded structure [4,5]. These observations support the common view that RNAs traverse rugged energy landscapes as they fold [6,7]. However, little is known about the true shape of these

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Section: How Atp-dependent Rna Chaperones Assist Foldingmentioning

confidence: 95%

Section: Reference Annotationsmentioning

confidence: 99%

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Chu

Herschlag

2008

Current Opinion in Structural Biology

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“…Furthermore, only a few DEAD-box proteins that have been tested demonstrate RNA unwinding activity with a generic RNA duplex substrate (Rocak and Linder, 2004;Cordin et al, 2006). Additionally, the presence of an Arg/Gly-rich C-terminal extension on PRH75 suggested, but did not demonstrate, a strand rewinding capacity (Yang et al, 2007). If the consequences of isoAsp formation on PRH75 enzymatic function are to be examined, it was imperative to demonstrate that the extrapolation of PRH75's function, based on structural similarity and motif presence, was valid ).…”

Section: Prh75mentioning

confidence: 98%

An Arabidopsis ATP-Dependent, DEAD-Box RNA Helicase Loses Activity upon IsoAsp Formation but Is Restored by PROTEIN ISOASPARTYL METHYLTRANSFERASE

et al. 2013

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“…The strand annealing reaction by DEAD box proteins is not the reverse of the unwinding reaction 60 . As a result, DEAD box proteins that catalyse both ATP-dependent duplex unwinding and ATP-independent strand annealing can promote RNA rearrangements that are much more complex than simple duplex unwinding or helix formation 60,61 .…”

Section: Atp Ground Statementioning

confidence: 99%

“…As a result, DEAD box proteins that catalyse both ATP-dependent duplex unwinding and ATP-independent strand annealing can promote RNA rearrangements that are much more complex than simple duplex unwinding or helix formation 60,61 . This ability is thought to be pivotal for the function of DEAD box proteins in RNA remodelling reactions, especially those that promote RNA chaperoning 61 .…”

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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DEAD-box-protein-assisted RNA Structure Conversion Towards and Against Thermodynamic Equilibrium Values

Cited by 35 publications

References 36 publications

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

Unwinding RNA's secrets: advances in the biology, physics, and modeling of complex RNAs

An Arabidopsis ATP-Dependent, DEAD-Box RNA Helicase Loses Activity upon IsoAsp Formation but Is Restored by PROTEIN ISOASPARTYL METHYLTRANSFERASE

From unwinding to clamping — the DEAD box RNA helicase family

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