DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA

Gao, Jun; Byrd, Alicia K.; Zybailov, Boris; Marecki, John C.; Guderyon, Michael; Edwards, A.; Chib, Shubeena; West, Kirk; Waldrip, Zachary J; Mackintosh, Samuel G.; Gao, Zhaofeng; Putnam, Andrea; Jankowsky, Eckhard; Raney, Kevin D.

doi:10.1039/c8cc10091h

Cited by 31 publications

(29 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A genome-wide study in yeast showed that Ded1 unwinds mRNA secondary structure in the 5′UTR during scanning of the 43S pre-initiation complex and prevents the use of near-cognate start codons that are proximal to such structures, allowing efficient translation of the main ORF [ 73 ]. DDX3X can also enhance IRES activity [ 74 ] and destabilize G-quadruplexes [ 75 , 76 ]. Intriguingly, recent studies propose a role of DDX3X in promoting [ 77 ] or repressing [ 78 ] repeat-associated, non-AUG (RAN) translation.…”

Section: De Novo Variants In Ddx3x Are Thmentioning

confidence: 99%

Mutations in genes encoding regulators of mRNA decapping and translation initiation: links to intellectual disability

Weil

Piton

Lessel

et al. 2020

Biochemical Society Transactions

View full text Add to dashboard Cite

Intellectual disability (ID) affects at least 1% of the population, and typically presents in the first few years of life. ID is characterized by impairments in cognition and adaptive behavior and is often accompanied by further delays in language and motor skills, as seen in many neurodevelopmental disorders (NDD). Recent widespread high-throughput approaches that utilize whole-exome sequencing or whole-genome sequencing have allowed for a considerable increase in the identification of these pathogenic variants in monogenic forms of ID. Notwithstanding this progress, the molecular and cellular consequences of the identified mutations remain mostly unknown. This is particularly important as the associated protein dysfunctions are the prerequisite to the identification of targets for novel drugs of these rare disorders. Recent Next-Generation sequencing-based studies have further established that mutations in genes encoding proteins involved in RNA metabolism are a major cause of NDD. Here, we review recent studies linking germline mutations in genes encoding factors mediating mRNA decay and regulators of translation, namely DCPS, EDC3, DDX6 helicase and ID. These RNA-binding proteins have well-established roles in mRNA decapping and/or translational repression, and the mutations abrogate their ability to remove 5′ caps from mRNA, diminish their interactions with cofactors and stabilize sub-sets of transcripts. Additional genes encoding RNA helicases with roles in translation including DDX3X and DHX30 have also been linked to NDD. Given the speed in the acquisition, analysis and sharing of sequencing data, and the importance of post-transcriptional regulation for brain development, we anticipate mutations in more such factors being identified and functionally characterized.

show abstract

Section: De Novo Variants In Ddx3x Are Thmentioning

confidence: 99%

Mutations in genes encoding regulators of mRNA decapping and translation initiation: links to intellectual disability

Weil

Piton

Lessel

et al. 2020

Biochemical Society Transactions

View full text Add to dashboard Cite

show abstract

“…Many helicases have been found to possess dual unwinding activities, acting on both DNA and RNA substrates. Thus far, there are seven helicases exhibiting RG4-unwinding activity and two of them have been identified to unwind DG4 structure as well (Booy et al., 2012, Chakraborty and Grosse, 2011, Gao et al., 2019). We then asked whether MOV10L1 can also work on DG4 substrate.…”

Section: Resultsmentioning

confidence: 99%

“…Increasing evidence indicates that intramolecular RNA G-quadruplex (RG4) motifs are biologically relevant structures, and their occurrence can play vital roles in many key cellular functions, including telomere homeostasis, gene expression, and pre-mRNA processing (Agarwala et al., 2015, Bugaut and Balasubramanian, 2012, Cammas and Millevoi, 2017, Fay et al., 2017, Millevoi et al., 2012, Rhodes and Lipps, 2015, Simone et al., 2015). Even though several helicases and nucleases have been shown to remove DNA G-quadruplex (DG4) structure and regulate cellular processes (Baran et al., 1997, Chen et al., 2018, Harrington et al., 1997, Mendoza et al., 2016, Sauer and Paeschke, 2017, Sun et al., 1998, Sun et al., 1999), only a few RNA helicases, so far, have been reported to be capable of unwinding RG4 structures in vitro (Booy et al., 2012, Chakraborty and Grosse, 2011, Creacy et al., 2008, Gao et al., 2019, McRae et al., 2017, Ribeiro de Almeida et al., 2018). One of the reasons is that RG4 is a thermodynamically stable structure compared with other forms of RNA, thereby in requirement of specialized RNA helicase to resolve it (Hardin et al., 2000).…”

Section: Introductionmentioning

confidence: 99%

MOV10L1 Binds RNA G-Quadruplex in a Structure-Specific Manner and Resolves It More Efficiently Than MOV10

Zhang

et al. 2019

iScience

View full text Add to dashboard Cite

Summary MOV10L1 and its paralog MOV10 are evolutionally conserved RNA helicases involved in distinct RNA regulatory pathways. The testis-specific MOV10L1 is essential for spermatogenesis and PIWI-interacting RNAs biogenesis, whereas MOV10 is ubiquitous and multifunctional. Although both proteins have been implied to correlate with RNA G-quadruplex (RG4) in vivo , their capabilities in binding and resolving RG4 and their respective biological significance remain unclear. Herein, we comprehensively characterize and compare the activities of these two helicases on various nucleic acid substrates in vitro , with a focus on RG4 structure. We find that both MOV10L1 and MOV10 are able to resolve RG4, with MOV10L1 being more efficient in that. In contrast to MOV10, MOV10L1 prefers to bind to a junction between single-stranded RNA and RG4, which is mediated by both its N and C termini. Furthermore, we show that RG4 unwinding by MOV10L1 facilitates the cleavage of this specific RNA structure by an endonuclease.

show abstract

“…DDX is an important ATP-dependent RNA helicase family, which exists in almost all prokaryotes and eukaryotes ( 11 ). Furthermore, DDX plays an important role in RNA metabolism, it is required for RNA functions, including gene transcription, RNA precursor mothering, ribosome synthesis, RNA output, translation initiation and RNA degradation ( 12 , 13 ). Several DDX RNA helicase subtypes have been reported to be abnormally expressed in various cancer types ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

DDX46 silencing inhibits cell proliferation by activating apoptosis and autophagy in cutaneous squamous cell carcinoma

et al. 2020

View full text Add to dashboard Cite

dead-Box Helicase 46 (ddX46) is an aTP-dependent rna helicase that plays a central role in transcription splicing and ribosome assembly. However, the role of ddX46 in cutaneous squamous cell carcinoma (cScc) remains to be elucidated. The aim of the present study was to investigate the role of ddX46 in cScc by assessing ddX46 expression levels in cScc tissues and cell lines. The effect of ddX46 silencing on cScc cell proliferation, apoptosis and autophagy were also analyzed. it was demonstrated that ddX46 was significantly overexpressed in cScc tissues and cells (P<0.05). Furthermore, it was found that ddX46 silencing could dramatically inhibit cell proliferation (P<0.05). Moreover, cell apoptosis and autophagy were activated in ddX46 silencing groups (P<0.05). Therefore, the present results suggested that ddX46 was overexpressed in cScc and that ddX46 silencing can inhibit cell proliferation by inducing apoptosis and activating autophagy. Thus, ddX46 may serve as a novel potential therapeutic target for cScc.

show abstract

DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA

Abstract: DEAD-box RNA helicases Dbp2, Ded1 and Mss116 bind to G-quadruplex nucleic acids and destabilize G-quadruplex RNA.

Cited by 31 publications

References 41 publications

Mutations in genes encoding regulators of mRNA decapping and translation initiation: links to intellectual disability

Mutations in genes encoding regulators of mRNA decapping and translation initiation: links to intellectual disability

MOV10L1 Binds RNA G-Quadruplex in a Structure-Specific Manner and Resolves It More Efficiently Than MOV10

DDX46 silencing inhibits cell proliferation by activating apoptosis and autophagy in cutaneous squamous cell carcinoma

Contact Info

Product

Resources

About