scholarly journals DEAD-Box Helicases: Sensors, Regulators, and Effectors for Antiviral Defense

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 181 ◽  
Author(s):  
Frances Taschuk ◽  
Sara Cherry
Keyword(s):  
Rna Binding ◽  
Viral Infections ◽  
Rna Binding Proteins ◽  
Large Family ◽  
Cellular Functions ◽  
Rna Helicases ◽  
Independent Manner ◽  
Dead Box ◽  
The Dead ◽  
Immune Sensing

DEAD-box helicases are a large family of conserved RNA-binding proteins that belong to the broader group of cellular DExD/H helicases. Members of the DEAD-box helicase family have roles throughout cellular RNA metabolism from biogenesis to decay. Moreover, there is emerging evidence that cellular RNA helicases, including DEAD-box helicases, play roles in the recognition of foreign nucleic acids and the modulation of viral infection. As intracellular parasites, viruses must evade detection by innate immune sensing mechanisms and degradation by cellular machinery while also manipulating host cell processes to facilitate replication. The ability of DEAD-box helicases to recognize RNA in a sequence-independent manner, as well as the breadth of cellular functions carried out by members of this family, lead them to influence innate recognition and viral infections in multiple ways. Indeed, DEAD-box helicases have been shown to contribute to intracellular immune sensing, act as antiviral effectors, and even to be coopted by viruses to promote their replication. However, our understanding of the mechanisms underlying these interactions, as well as the cellular roles of DEAD-box helicases themselves, is limited in many cases. We will discuss the diverse roles that members of the DEAD-box helicase family play during viral infections.

scholarly journals PRH75, a new nucleus-localized member of the DEAD-box protein family from higher plants.

1997 ◽  
Vol 17 (4) ◽  
pp. 2257-2265 ◽  
Author(s):  
Z J Lorković ◽  
R G Herrmann ◽  
R Oelmüller
Keyword(s):  
Amino Acids ◽  
Rna Binding ◽  
Protein Family ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Rna Helicases ◽  
Nuclear Targeting ◽  
Dead Box ◽  
Cell Extracts ◽  
The Dead

The putative RNA helicases of the DEAD-box protein family are involved in pre-mRNA splicing, rRNA maturation, ribosome assembly, and translation. Members of this protein family have been identified in organisms from Escherichia coli to humans, but except for the translation initiation factor 4A, there have been no reports on the characterization of other DEAD-box proteins from plants. Here we report on a novel member of the DEAD-box protein family, the plant RNA helicase 75 (PRH75). PRH75 is localized in the nucleus and contains two domains for RNA binding. One is located at the C terminus and is similar to RGG RNA-binding domains of nucleus-localized RNA-binding proteins. The other one is located between amino acids 308 and 622, a region containing the conserved motif VI characteristic of DEAD-box proteins and known as the RNA-binding site of eIF-4A. The N-terminal 81 amino acids are sufficient for nuclear targeting of the protein. Northern and Western blot analyses show that PRH75 is mainly expressed in young and rapidly developing tissues. The purified recombinant PRH75 has a weak ATPase activity which is barely stimulated by RNA ligands. The fractionation of spinach whole-cell extracts by glycerol gradient centrifugation and gel filtration on a Superdex 200 column shows that the protein exists in a complex of about 500 kDa. Possible biological functions of PRH75 as well as structure-function relationships in the context of its modular primary structure are discussed.

scholarly journals Dynamics of the DEAD-box ATPase Prp5 RecA-like domains provide a conformational switch during spliceosome assembly

2019 ◽  
Vol 47 (20) ◽  
pp. 10842-10851 ◽  
Author(s):  
David H Beier ◽  
Tucker J Carrocci ◽  
Clarisse van der Feltz ◽  
U Sandy Tretbar ◽  
Joshua C Paulson ◽  
...  
Keyword(s):  
Single Molecule ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Conformational Dynamics ◽  
Spliceosome Assembly ◽  
Single Molecule Fret ◽  
Dead Box ◽  
U2 Snrnp ◽  
The Dead

Abstract The DEAD-box family of proteins are ATP-dependent, RNA-binding proteins implicated in many aspects of RNA metabolism. Pre-mRNA splicing in eukaryotes requires three DEAD-box ATPases (Prp5, Prp28 and Sub2), the molecular mechanisms of which are poorly understood. Here, we use single molecule FRET (smFRET) to study the conformational dynamics of yeast Prp5. Prp5 is essential for stable association of the U2 snRNP with the intron branch site (BS) sequence during spliceosome assembly. Our data show that the Prp5 RecA-like domains undergo a large conformational rearrangement only in response to binding of both ATP and RNA. Mutations in Prp5 impact the fidelity of BS recognition and change the conformational dynamics of the RecA-like domains. We propose that BS recognition during spliceosome assembly involves a set of coordinated conformational switches among U2 snRNP components. Spontaneous toggling of Prp5 into a stable, open conformation may be important for its release from U2 and to prevent competition between Prp5 re-binding and subsequent steps in spliceosome assembly.

scholarly journals The role of interactions of long non-coding RNAs and heterogeneous nuclear ribonucleoproteins in regulating cellular functions

2017 ◽  
Vol 474 (17) ◽  
pp. 2925-2935 ◽  
Author(s):  
Xinghui Sun ◽  
Mohamed Sham Shihabudeen Haider Ali ◽  
Matthew Moran
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genomic Structure ◽  
Large Family ◽  
Research Area ◽  
Nucleic Acid Metabolism ◽  
Cellular Functions ◽  
Glucose And Lipid Metabolism ◽  
Heterogeneous Nuclear Ribonucleoproteins ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are emerging as critical regulators of various biological processes and human diseases. The mechanisms of action involve their interactions with proteins, RNA and genomic DNA. Most lncRNAs display strong nuclear localization. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large family of RNA-binding proteins that are important for multiple aspects of nucleic acid metabolism. hnRNPs are also predominantly expressed in the nucleus. This review discusses the interactions of lncRNAs and hnRNPs in regulating gene expression at transcriptional and post-transcriptional levels or by changing genomic structure, highlighting their involvements in glucose and lipid metabolism, immune response, DNA damage response, and other cellular functions. Toward the end, several techniques that are used to identify lncRNA binding partners are summarized. There are still many questions that need to be answered in this relatively new research area, which might provide novel targets to control the biological outputs of cells in response to different stimuli.

scholarly journals DEAD-Box RNA Helicases and Genome Stability

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1471
Author(s):  
Michael Cargill ◽  
Rasika Venkataraman ◽  
Stanley Lee
Keyword(s):  
Dna Damage ◽  
Therapeutic Relationship ◽  
Genome Stability ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genomic Stability ◽  
Rna Helicase ◽  
Rna Helicases ◽  
Dead Box ◽  
Insight Into

DEAD-box RNA helicases are important regulators of RNA metabolism and have been implicated in the development of cancer. Interestingly, these helicases constitute a major recurring family of RNA-binding proteins important for protecting the genome. Current studies have provided insight into the connection between genomic stability and several DEAD-box RNA helicase family proteins including DDX1, DDX3X, DDX5, DDX19, DDX21, DDX39B, and DDX41. For each helicase, we have reviewed evidence supporting their role in protecting the genome and their suggested mechanisms. Such helicases regulate the expression of factors promoting genomic stability, prevent DNA damage, and can participate directly in the response and repair of DNA damage. Finally, we summarized the pathological and therapeutic relationship between DEAD-box RNA helicases and cancer with respect to their novel role in genome stability.

scholarly journals Contribution of DEAH-box protein DHX16 in human pre-mRNA splicing

2010 ◽  
Vol 429 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Marieta Gencheva ◽  
Mitsuo Kato ◽  
Alain N.S. Newo ◽  
Ren-Jang Lin
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mrna Splicing ◽  
Dominant Negative ◽  
Helicase Domain ◽  
Rna Helicases ◽  
Mutant Proteins ◽  
Dead Box ◽  
Nuclear Extracts

Studies of mammalian splicing factors are often focused on small nuclear ribonucleoproteins or regulatory RNA-binding proteins, such as hnRNP (heterogeneous nuclear ribonucleoprotein) and SR proteins (serine/arginine-rich proteins); however, much less is known about the contribution of DExD/H-box proteins or RNA helicases in mammalian pre-mRNA splicing. The human DEAH-box protein DHX16 [also known as DBP2 (DEAD-box protein 2)], is homologous with Caenorhabditis elegans Mog-4, Schizosaccharomyces pombe Prp8 and Saccharomyces cerevisiae Prp2. In the present study, we show that DHX16 is required for pre-mRNA splicing after the formation of a pre-catalytic spliceosome. We found that anti-DHX16 antiserum inhibited the splicing reaction in vitro and the antibody immunoprecipitated pre-mRNA, splicing intermediates and spliceosomal small nuclear RNAs. Cells that expressed DHX16 that had a mutation in the helicase domain accumulated unspliced intron-containing minigene transcripts. Nuclear extracts isolated from the dominant-negative DHX16-G724N-expressing cells formed splicing complex B, but were impaired in splicing. Adding extracts containing DHX16-G724N or DHX16-S552L mutant proteins to HeLa cell nuclear extracts resulted in reduced splicing, indicating that the mutant protein directly inhibited splicing in vitro. Therefore our results show that DHX16 is needed for human pre-mRNA splicing at a step analogous to that mediated by the S. cerevisiae spliceosomal ATPase Prp2.

scholarly journals CPB-3 and CGH-1 localize to motile particles within dendrites in C. elegans PVD sensory neurons

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kathrin Spendier ◽  
Eugenia C. Olesnicky ◽  
Daniel Forand ◽  
Margaret Wolf ◽  
Darrell J. Killian
Keyword(s):  
Translational Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Helicases ◽  
Cytoplasmic Polyadenylation ◽  
C Elegans ◽  
Mrna Targets ◽  
Dead Box ◽  
Dendrite Development

Abstract Objective RNA-binding proteins (RBPs) are important regulators of gene expression that influence mRNA splicing, stability, localization, transport, and translational control. In particular, RBPs play an important role in neurons, which have a complex morphology. Previously, we showed that there are many RBPs that play a conserved role in dendrite development in Drosophila dendritic arborization neurons and Caenorhabditis elegans (C. elegans) PVD neurons including the cytoplasmic polyadenylation element binding proteins (CPEBs), Orb in Drosophila and CPB-3 in C. elegans, and the DEAD box RNA helicases, Me31B in Drosophila and CGH-1 in C. elegans. During these studies, we observed that fluorescently-labeled CPB-3 and CGH-1 localize to cytoplasmic particles that are motile, and our research aims to further characterize these RBP-containing particles in live neurons. Results Here we extend on previous work to show that CPB-3 and CGH-1 localize to motile particles within dendrites that move at a speed consistent with microtubule-based transport. This is consistent with a model in which CPB-3 and CGH-1 influence dendrite development through the transport and localization of their mRNA targets. Moreover, CPB-3 and CGH-1 rarely localize to the same particles suggesting that these RBPs function in discrete ribonucleoprotein particles (RNPs) that may regulate distinct mRNAs.

scholarly journals Association of the Cold Shock DEAD-Box RNA Helicase RhlE to the RNA Degradosome in Caulobacter crescentus

2017 ◽  
Vol 199 (13) ◽  
Author(s):  
Angel A. Aguirre ◽  
Alexandre M. Vicente ◽  
Steven W. Hardwick ◽  
Daniela M. Alvelos ◽  
Ricardo R. Mazzon ◽  
...  
Keyword(s):  
Low Temperature ◽  
Caulobacter Crescentus ◽  
Immunoblot Analysis ◽  
Rna Helicase ◽  
Rnase E ◽  
Rna Helicases ◽  
Content Type ◽  
Dead Box ◽  
Rna Degradosome ◽  
The Dead

ABSTRACT In diverse bacterial lineages, multienzyme assemblies have evolved that are central elements of RNA metabolism and RNA-mediated regulation. The aquatic Gram-negative bacterium Caulobacter crescentus, which has been a model system for studying the bacterial cell cycle, has an RNA degradosome assembly that is formed by the endoribonuclease RNase E and includes the DEAD-box RNA helicase RhlB. Immunoprecipitations of extracts from cells expressing an epitope-tagged RNase E reveal that RhlE, another member of the DEAD-box helicase family, associates with the degradosome at temperatures below those optimum for growth. Phenotype analyses of rhlE, rhlB, and rhlE rhlB mutant strains show that RhlE is important for cell fitness at low temperature and its role may not be substituted by RhlB. Transcriptional and translational fusions of rhlE to the lacZ reporter gene and immunoblot analysis of an epitope-tagged RhlE indicate that its expression is induced upon temperature decrease, mainly through posttranscriptional regulation. RNase E pulldown assays show that other proteins, including the transcription termination factor Rho, a second DEAD-box RNA helicase, and ribosomal protein S1, also associate with the degradosome at low temperature. The results suggest that the RNA degradosome assembly can be remodeled with environmental change to alter its repertoire of helicases and other accessory proteins. IMPORTANCE DEAD-box RNA helicases are often present in the RNA degradosome complex, helping unwind secondary structures to facilitate degradation. Caulobacter crescentus is an interesting organism to investigate degradosome remodeling with change in temperature, because it thrives in freshwater bodies and withstands low temperature. In this study, we show that at low temperature, the cold-induced DEAD-box RNA helicase RhlE is recruited to the RNA degradosome, along with other helicases and the Rho protein. RhlE is essential for bacterial fitness at low temperature, and its function may not be complemented by RhlB, although RhlE is able to complement for rhlB loss. These results suggest that RhlE has a specific role in the degradosome at low temperature, potentially improving adaptation to this condition.

scholarly journals The embryonic RNA helicase gene (ERH): a new member of the DEAD box family of RNA helicases

1995 ◽  
Vol 308 (3) ◽  
pp. 839-846 ◽  
Author(s):  
J Sowden ◽  
W Putt ◽  
K Morrison ◽  
R Beddington ◽  
Y Edwards
Keyword(s):  
Expression Profile ◽  
Sequence Similarity ◽  
Rna Helicase ◽  
Chromosome 1 ◽  
Rna Helicases ◽  
High Sequence Similarity ◽  
Dead Box ◽  
Isolation And Characterization ◽  
Helicase Gene ◽  
The Dead

DEAD box proteins share several highly conserved motifs including the characteristic Asp-Glu-Ala-Asp (D-E-A-D in the amino acid single-letter code) motif and have established or putative ATP-dependent RNA helicase activity. These proteins are implicated in a range of cellular processes that involve regulation of RNA function, including translation initiation, RNA splicing and ribosome assembly. Here we describe the isolation and characterization of an embryonic RNA helicase gene, ERH, which maps to mouse chromosome 1 and encodes a new member of the DEAD box family of proteins. The predicted ERH protein shows high sequence similarity to the testes-specific mouse PL10 and to the maternally acting Xenopus An3 helicase proteins. The ERH expression profile is similar, to that of An3, which localizes to the animal hemisphere of oocytes and is abundantly expressed in the embryo. ERH is expressed in oocytes and is a ubiquitous mRNA in the 9 days-post-conception embryo, and at later stages of development shows a more restricted pattern of expression in brain and kidney. The similarities in sequence and in expression profile suggest that ERH is the murine equivalent of the Xenopus An3 gene, and we propose that ERH plays a role in translational activation of mRNA in the oocyte and early embryo.

scholarly journals The DEAD-Box RNA Helicases of Bacillus subtilis as a Model to Evaluate Genetic Compensation Among Duplicate Genes

2018 ◽  
Vol 9 ◽  
Author(s):  
José Antonio González-Gutiérrez ◽  
Diana Fabiola Díaz-Jiménez ◽  
Itzel Vargas-Pérez ◽  
Gabriel Guillén-Solís ◽  
Jörg Stülke ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Duplicate Genes ◽  
Rna Helicases ◽  
Dead Box ◽  
The Dead ◽  
Genetic Compensation
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