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DEAD helicase

Ewan K S McRae, David E Davidson, Steven J Dupas, Sean A McKenna
Guanine quadruplexes can form in both DNA and RNA and influence many biological processes through various protein interactions. The DEAD-box RNA helicase protein DDX21 has been shown to bind and remodel RNA quadruplexes but little is known about its specificity for different quadruplex species. Previous reports have suggested DDX21 may interact with telomeric repeat containing RNA quadruplex (TERRA), an integral component of the telomere that contributes to telomeric heterochromatin formation and telomere length regulation...
June 12, 2018: Biochimica et Biophysica Acta
P Doñate-Macián, J Jungfleisch, G Pérez-Vilaró, F Rubio-Moscardo, A Perálvarez-Marín, J Diez, M A Valverde
Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca2+ influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation...
June 13, 2018: Nature Communications
Daniel H Lin, Ana R Correia, Sarah W Cai, Ferdinand M Huber, Claudia A Jette, André Hoelz
The nuclear pore complex (NPC) controls the passage of macromolecules between the nucleus and cytoplasm, but how the NPC directly participates in macromolecular transport remains poorly understood. In the final step of mRNA export, the DEAD-box helicase DDX19 is activated by the nucleoporins Gle1, Nup214, and Nup42 to remove Nxf1•Nxt1 from mRNAs. Here, we report crystal structures of Gle1•Nup42 from three organisms that reveal an evolutionarily conserved binding mode. Biochemical reconstitution of the DDX19 ATPase cycle establishes that human DDX19 activation does not require IP6 , unlike its fungal homologs, and that Gle1 stability affects DDX19 activation...
June 13, 2018: Nature Communications
Spyridon Stavrou, Alexya N Aguilera, Kristin Blouch, Susan R Ross
Host recognition of viral nucleic acids generated during infection leads to the activation of innate immune responses essential for early control of virus. Retrovirus reverse transcription creates numerous potential ligands for cytosolic host sensors that recognize foreign nucleic acids, including single-stranded RNA (ssRNA), RNA/DNA hybrids, and double-stranded DNA (dsDNA). We and others recently showed that the sensors cyclic GMP-AMP synthase (cGAS), DEAD-box helicase 41 (DDX41), and members of the Aim2-like receptor (ALR) family participate in the recognition of retroviral reverse transcripts...
June 5, 2018: MBio
Kiyoko Tanaka, Narumi Ikeda, Kazuya Miyashita, Hideko Nuriya, Takahiko Hara
DDX1, a member of the DEAD box RNA helicase family, plays a critical role in testicular tumors. However, it remains to be clarified whether DDX1 is involved in other types of malignant tumors such as colorectal cancer. We disrupted the DDX1 gene in a human colorectal cancer cell line LoVo using the CRISPR/Cas9-mediated gene-targeting system. DDX1-KO LoVo cells exhibited a much slower growth rate, produced fewer colonies in soft agar medium, and generated smaller solid tumors in nude mice than parental LoVo cells...
June 5, 2018: Cancer Science
Tong Zhang, Zhenjiang Ma, Lijuan Liu, Jian Sun, Hui Tang, Bing Zhang, Ying Zou, Heping Li
Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide; however, the molecular mechanisms regulating HCC progression remain largely unknown. In this study, we determined the role of DDX39 which a DEAD-box RNA helicase in HCC progression, and found DDX39 was upregulated in HCC tissues and cells, DDX39 expression was positive correlated with advanced clinical stage, survival analysis showed patients with high-DDX39 levels had poor outcome, it was an independent prognostic factor...
June 4, 2018: Cell Death & Disease
Mirco Glitscher, Kiyoshi Himmelsbach, Kathrin Woytinek, Reimar Johne, Andreas Reuter, Jelena Spiric, Luisa Schwaben, Arnold Grünweller, Eberhard Hildt
Every year, there are about 20 Mio hepatitis E virus (HEV) infections and 60,000 deaths that are associated with HEV worldwide. At the present, there exists no specific therapy for HEV. The natural compound silvestrol has a potent antiviral effect against the (-)-strand RNA-virus Ebola virus, and also against the (+)-strand RNA viruses Corona-, Picorna-, and Zika virus. The inhibitory effect on virus spread is due to an inhibition of the DEAD-box RNA helicase eIF4A, which is required to unwind structured 5'-untranslated regions (UTRs)...
June 2, 2018: Viruses
Tara L Peters, Joseph Tillotson, Alison M Yeomans, Sarah Wilmore, Elizabeth Lemm, Carlos Jiménez-Romero, Luis A Amador, Lingxiao Li, Amit Dipak Amin, Praechompoo Pongtornpipat, Christopher J Zerio, Andrew J Ambrose, Gillian Paine-Murrieta, Patricia Greninger, Francisco Vega, Cyril H Benes, Graham Packham, Abimael D Rodriguez, Eli Chapman, Jonathan H Schatz
PURPOSE: The DEAD-box RNA helicase eIF4A1 carries out the key enzymatic step of cap-dependent translation initiation and is a well-established target for cancer therapy, but no drug against it has entered evaluation in patients. We identified and characterized a natural compound with broad antitumor activities that emerged from the first target-based screen to identify novel eIF4A1 inhibitors. EXPERIMENTAL DESIGN: We tested potency and specificity of the marine compound elatol vs...
May 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Zhengzheng Duan, Ping Ping, Guishuan Wang, Xiansheng Zhang, Fei Sun
Intermediate-size noncoding RNAs (imsncRNAs) have been shown to play important regulatory roles in the development of several eukaryotic organisms. In this research, we selected imsnc761 as a research target. Expression analyses in a previous study showed that imsnc761 was downregulated in maturation-arrested testis tissue compared with the level in normal controls. In this study, we found that imsnc761 could interact with DEAD-box helicase 6 (DDX6) to induce NT2 cell apoptosis and proliferation inhibition via the p53 pathway...
May 16, 2018: Bioscience Reports
Masumi Okamura, Yasutaka Yamanaka, Maki Shigemoto, Yuya Kitadani, Yuhko Kobayashi, Taiho Kambe, Masaya Nagao, Issei Kobayashi, Katsuzumi Okumura, Seiji Masuda
DBP5, also known as DDX19, GLE1 and inositol hexakisphosphate (IP6) function in messenger RNA (mRNA) export at the cytoplasmic surface of the nuclear pore complex in eukaryotic cells. DBP5 is a DEAD-box RNA helicase, and its activity is stimulated by interactions with GLE1 and IP6. In addition, these three factors also have unique role(s). To investigate how these factors influenced the cytoplasmic mRNA expression and cell phenotype change, we performed RNA microarray analysis to detect the effect and function of DBP5, GLE1 and IP6 on the cytoplasmic mRNA expression...
2018: PloS One
Vanessa Meier-Stephenson, Tyler Mrozowich, Mimi Pham, Trushar R Patel
Viruses hijack the host cell machinery and recruit host proteins to aid their replication. Several host proteins also play vital roles in inhibiting viral replication. Emerging class of host proteins central to both of these processes are the DEAD-box helicases: a highly conserved family of ATP-dependent RNA helicases, bearing a common D-E-A-D (Asp-Glu-Ala-Asp) motif. They play key roles in numerous cellular processes, including transcription, splicing, miRNA biogenesis and translation. Though their sequences are highly conserved, these helicases have quite diverse roles in the cell...
May 9, 2018: Biotechnology & Genetic Engineering Reviews
Ming-Rong Cao, Ze-Ping Han, Ji-Ming Liu, Yu-Guang Li, Yu-Bing Lv, Jia-Bin Zhou, Jin-Hua He
Computational analysis and bioinformatics have significantly advanced the ability of researchers to process and analyze biological data. Molecular data from human and model organisms may facilitate drug target validation and identification of biomarkers with increased predictive accuracy. The aim of the present study was to investigate the function of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) using online databases, and to predict their regulatory mechanism. HCC-associated lncRNAs, their downstream transcription factors and microRNAs (miRNAs/miRs), as well as the HCC-associated target genes, were identified using online databases...
May 2018: Oncology Letters
Wen Zhong, Zonghong Li, Maoge Zhou, Tao Xu, You Wang
DEAD-box helicase 1 (DDX1) is a multifunction protein involved in diverse cellular processes including transcription, viral replication, mRNA/miRNA processing, and tRNA splicing. Here, we report a novel function of DDX1 in mRNA alternative splicing in pancreatic β cells. By performing integrated data analysis of high-throughput RNA sequencing (RNA-Seq), and cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq), we identify hundreds of alternative splicing genes that are targeted by DDX1...
June 7, 2018: Biochemical and Biophysical Research Communications
Ghazala Nawaz, Kwanuk Lee, Su Jung Park, Yeon-Ok Kim, Hunseung Kang
Although the roles of many DEAD-box RNA helicases (RHs) have been determined in the nucleus as well as in cytoplasm during stress responses, the importance of chloroplast-targeted DEAD-box RHs in stress response remains largely unknown. In this study, we determined the function of BrRH22, a chloroplast-targeted DEAD-box RH in cabbage (Brassica rapa), in abiotic stress responses. The expression of BrRH22 was markedly increased by drought, heat, salt, or cold stress and by ABA treatment, but was largely decreased by UV stress...
June 2018: Plant Physiology and Biochemistry: PPB
Wenyu Cheng, Guohua Chen, Huaijie Jia, Xiaobing He, Zhizhong Jing
Asp-Glu-Ala-Asp (DEAD)-box polypeptide 5 (DDX5), also called p68, is a prototypical member of the large ATP-dependent RNA helicases family and is known to participate in all aspects of RNA metabolism ranging from transcription to translation, RNA decay, and miRNA processing. The roles of DDX5 in cell cycle regulation, tumorigenesis, apoptosis, cancer development, adipogenesis, Wnt-β-catenin signaling, and viral infection have been established. Several RNA viruses have been reported to hijack DDX5 to facilitate various steps of their replication cycles...
April 9, 2018: International Journal of Molecular Sciences
Peter Hoch-Kraft, Robin White, Stefan Tenzer, Eva-Maria Krämer-Albers, Jacqueline Trotter, Constantin Gonsior
In the central nervous system, oligodendroglial expression of myelin basic protein (MBP) is crucial for the assembly and structure of the myelin sheath. MBP synthesis is tightly regulated in space and time, particularly at the post-transcriptional level. We have identified the DEAD-box RNA helicase DDX5 (also known as p68) in a complex with Mbp mRNA in oligodendroglial cells. Expression of DDX5 is highest in progenitor cells and immature oligodendrocytes, where it localizes to heterogeneous populations of cytoplasmic ribonucleoprotein (RNP) complexes associated with Mbp mRNA in the cell body and processes...
May 1, 2018: Journal of Cell Science
Xian Duo Zhang, Jia Yun Sun, Yuan Yuan You, Jian Bo Song, Zhi Min Yang
RNA helicases play crucial roles in RNA splicing, transport, editing and degradation, protein translation initiation and siRNA-mediated gene silencing. However, knowledge about their functionality in rapeseed (Brassica napus) is rare. In the study, we identified and annotated 271 RNA helicase genes from B. napus using bioinformatics and high-throughput RNA-sequencing (RNA-seq). Three subfamilies DEAD-box, DEAH-box, or DExD/H-box have been identified. One hundred and ninety-five RNA helicases were confirmed by RNA-seq and 49 were identified to differentially respond to cadmium (Cd) stress (> 1...
August 15, 2018: Ecotoxicology and Environmental Safety
Lamya El Mortaji, Sylvie Aubert, Eloïse Galtier, Christine Schmitt, Karine Anger, Yulia Redko, Yves Quentin, Hilde De Reuse
Present in every kingdom of life, generally in multiple copies, DEAD-box RNA helicases are specialized enzymes that unwind RNA secondary structures. They play major roles in mRNA decay, ribosome biogenesis, and adaptation to cold temperatures. Most bacteria have multiple DEAD-box helicases that present both specialized and partially redundant functions. By using phylogenomics, we revealed that the Helicobacter genus, including the major gastric pathogen H. pylori , is among the exceptions, as it encodes a sole DEAD-box RNA helicase...
March 27, 2018: MBio
Fabian Elgner, Catarina Sabino, Michael Basic, Daniela Ploen, Arnold Grünweller, Eberhard Hildt
The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (-)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5'-UTRs) of several proto-oncogenes and thereby facilitate their translation...
March 27, 2018: Viruses
Woonhee Baek, Chae Woo Lim, Sung Chul Lee
Abscisic acid (ABA) is major plant hormone involved in regulating abiotic stress responses. Several studies have established that an ABA-signalling transduction pathway-from ABA perception to response-functions in plant cells. The group A PP2Cs constitute core components of ABA signalling, and they negatively regulate ABA signalling and stress responses. Recent studies have identified and functionally analysed regulators of PP2C activity; however, the precise regulatory mechanisms remain unclear. In the present study, we used a yeast 2-hybrid (Y2H) screening analysis to identify the DEAD-box RNA helicase RH8, which interacted with PP2CA in the nucleus...
March 25, 2018: Plant, Cell & Environment
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