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https://www.readbyqxmd.com/read/29165676/structure-of-mycobacterial-3-to-5-rna-dna-helicase-lhr-bound-to-a-ssdna-tracking-strand-highlights-distinctive-features-of-a-novel-family-of-bacterial-helicases
#1
Anam Ejaz, Heather Ordonez, Agata Jacewicz, Ryan Ferrao, Stewart Shuman
Mycobacterial Lhr is a DNA damage-inducible superfamily 2 helicase that uses adenosine triphosphate (ATP) hydrolysis to drive unidirectional 3'-to-5' translocation along single-stranded DNA (ssDNA) and to unwind RNA:DNA duplexes en route. ATPase, translocase and helicase activities are encompassed within the N-terminal 856-amino acid segment. The crystal structure of Lhr-(1-856) in complex with AMPPNP•Mg2+ and ssDNA defines a new helicase family. The enzyme comprises two N-terminal RecA-like modules, a winged helix (WH) domain and a unique C-terminal domain...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165589/ns3-helicase-from-dengue-virus-specifically-recognizes-viral-rna-sequence-to-ensure-optimal-replication
#2
Crystall M D Swarbrick, Chandrakala Basavannacharya, Kitti W K Chan, Shu-Ann Chan, Daljit Singh, Na Wei, Wint Wint Phoo, Dahai Luo, Julien Lescar, Subhash G Vasudevan
The protein-RNA interactions within the flavivirus replication complex (RC) are not fully understood. Our structure of dengue virus NS3 adenosine triphosphatase (ATPase)/helicase bound to the conserved 5' genomic RNA 5'-AGUUGUUAGUCU-3' reveals that D290 and R538 make specific interactions with G2 and G5 bases respectively. We show that single-stranded 12-mer RNA stimulates ATPase activity of NS3, however the presence of G2 and G5 leads to significantly higher activation. D290 is adjacent to the DEXH motif found in SF2 helicases like NS3 and interacts with R387, forming a molecular switch that activates the ATPase site upon RNA binding...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165424/functional-5-utr-mrna-structures-in-eukaryotic-translation-regulation-and-how-to-find-them
#3
REVIEW
Kathrin Leppek, Rhiju Das, Maria Barna
RNA molecules can fold into intricate shapes that can provide an additional layer of control of gene expression beyond that of their sequence. In this Review, we discuss the current mechanistic understanding of structures in 5' untranslated regions (UTRs) of eukaryotic mRNAs and the emerging methodologies used to explore them. These structures may regulate cap-dependent translation initiation through helicase-mediated remodelling of RNA structures and higher-order RNA interactions, as well as cap-independent translation initiation through internal ribosome entry sites (IRESs), mRNA modifications and other specialized translation pathways...
November 22, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29164525/heat-shock-factor-4-regulates-the-expression-of-hsp25-and-alpha-b-crystallin-by-associating-with-dexd-h-box-rna-helicase-uap56
#4
Xiukun Cui, Wenxiu Han, Jing Li, Riping Feng, Zheng Zhou, JiuLi Han, Mengyuan Li, Shuangfeng Wang, Wanting Zhang, Qin Lei, Jun Zhang, Yutiao Liu, Yanzhong Hu
Heat shock factor 4 controls the transcription of small heat shock proteins (e.g., HSP25, alpha B-cyrstallin, and r-crystallin), that play important roles in modulating lens proteostasis. However, the molecular mechanism underlying HSF4-mediated transcription is still unclear. Using yeast two hybrid, we found that HSF4 interacts with the ATP-dependent DEXD/H-box RNA helicase UAP56, and their interaction in lens epithelial cell line was further confirmed by GST-pull down assay. UAP56 is a vital regulator of pre-mRNA splicing and mature mRNA nuclear export...
November 21, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29164104/targeting-dengue-virus-ns-3-helicase-by-ligand-based-pharmacophore-modeling-and-structure-based-virtual-screening
#5
Sobia A Halim, Shanza Khan, Ajmal Khan, Abdul Wadood, Fazal Mabood, Javid Hussain, Ahmed Al-Harrasi
Dengue fever is an emerging public health concern, with several million viral infections occur annually, for which no effective therapy currently exist. Non-structural protein 3 (NS-3) Helicase encoded by the dengue virus (DENV) is considered as a potential drug target to design new and effective drugs against dengue. Helicase is involved in unwinding of dengue RNA. This study was conducted to design new NS-3 Helicase inhibitor by in silico ligand- and structure based approaches. Initially ligand-based pharmacophore model was generated that was used to screen a set of 1201474 compounds collected from ZINC Database...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29163777/dhx15-is-associated-with-poor-prognosis-in-acute-myeloid-leukemia-aml-and-regulates-cell-apoptosis-via-the-nf-kb-signaling-pathway
#6
Lili Pan, Yang Li, Hai-Ying Zhang, Yi Zheng, Xiao-Li Liu, Zheng Hu, Yi Wang, Jing Wang, Yuan-Hua Cai, Qiao Liu, Wan-Ling Chen, Ying Guo, Yuan-Mao Huang, Feng Qian, Li Jin, Jiucun Wang, Shao-Yuan Wang
The role of DHX15, a newly identified DEAH-box RNA helicase, in leukemogenesis remains elusive. Here, we identified a recurrent mutation in DHX15 (NM_001358:c.664C>G: p.(R222G)) in one familial AML patient and 4/240 sporadic AML patients. Additionally, DHX15 was commonly overexpressed in AML patients and associated with poor overall survival (OS) (P=0.019) and relapse-free survival (RFS) (P=0.032). In addition, we found a distinct expression pattern of DHX15. DHX15 was highly expressed in hematopoietic stem cells and leukemia cells but was lowly expressed in mature blood cells...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150525/distinct-rna-unwinding-mechanisms-of-dead-box-and-deah-box-rna-helicase-proteins-in-remodeling-structured-rnas-and-rnps
#7
REVIEW
Benjamin Gilman, Pilar Tijerina, Rick Russell
Structured RNAs and RNA-protein complexes (RNPs) fold through complex pathways that are replete with misfolded traps, and many RNAs and RNPs undergo extensive conformational changes during their functional cycles. These folding steps and conformational transitions are frequently promoted by RNA chaperone proteins, notably by superfamily 2 (SF2) RNA helicase proteins. The two largest families of SF2 helicases, DEAD-box and DEAH-box proteins, share evolutionarily conserved helicase cores, but unwind RNA helices through distinct mechanisms...
November 17, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29149092/analysis-of-the-roles-of-the-arabidopsis-nmat2-and-pmh2-proteins-provided-with-new-insights-into-the-regulation-of-group-ii-intron-splicing-in-land-plant-mitochondria
#8
Michal Zmudjak, Sofia Shevtsov, Laure D Sultan, Ido Keren, Oren Ostersetzer-Biran
Plant mitochondria are remarkable with respect to the presence of numerous group II introns which reside in many essential genes. The removal of the organellar introns from the coding genes they interrupt is essential for respiratory functions, and is facilitated by different enzymes that belong to a diverse set of protein families. These include maturases and RNA helicases related proteins that function in group II intron splicing in different organisms. Previous studies indicate a role for the nMAT2 maturase and the RNA helicase PMH2 in the maturation of different pre-RNAs in Arabidopsis mitochondria...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29146961/identification-of-host-dead-box-rna-helicases-that-regulate-cellular-tropism-of-oncolytic-myxoma-virus-in-human-cancer-cells
#9
Masmudur M Rahman, Eugenie Bagdassarian, Mohamed A M Ali, Grant McFadden
Myxoma virus (MYXV), a Leporipoxvirus, is being developed as an oncolytic virotherapeutic for the treatment of a variety of human cancers. MYXV tropism for human cancer cells is largely mediated by intracellular signaling networks that regulate viral replication or innate antiviral response pathways. Thus, MYXV is fully or partially permissive for the majority of human cancer cells that harbor defects in antiviral signaling, but a minority are nonpermissive because the virus infection aborts before its completion...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29144498/corrigendum-the-rna-helicase-ddx46-inhibits-innate-immunity-by-entrapping-m-6-a-demethylated-antiviral-transcripts-in-the-nucleus
#10
Qingliang Zheng, Jin Hou, Ye Zhou, Zhenyang Li, Xuetao Cao
This corrects the article DOI: 10.1038/ni.3830.
November 16, 2017: Nature Immunology
https://www.readbyqxmd.com/read/29142128/interaction-between-a-unique-minor-protein-and-a-major-capsid-protein-of-bluetongue-virus-controls-virus-infectivity
#11
Eiko Matsuo, Kiyoshi Yamazaki, Hiroki Tsuruta, Polly Roy
Among the Reoviridae family of double-stranded RNA viruses, only members of the Orbivirus genus possess a unique structural protein, termed VP6, within their particles. Bluetongue virus (BTV), an important livestock pathogen, is the prototype Orbivirus The BTV VP6 is an ATP-dependent RNA helicase and it is indispensable for virus replication. In this report, we investigated how VP6 might be recruited to the virus capsid and whether the BTV structural protein VP3, which forms the internal layer of the virus capsid core, is involved in VP6 recruitment...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29140168/revisiting-the-roles-of-tobamovirus-replicase-complex-proteins-in-viral-replication-and-silencing-suppression
#12
Nachelli Malpica-López, Rajendran Rajeswaran, Daria Beknazariants, Jonathan Seguin, Victor Golyaev, Laurent Farinelli, Mikhail M Pooggin
Tobamoviral replicase possesses an RNA-dependent RNA polymerase (RDR) domain and is translated from genomic (g)RNA via a stop codon readthrough mechanism at a one-to-ten ratio relative to a shorter protein lacking the RDR domain. The two proteins share methyltransferase and helicase domains and form a heterodimer implicated in gRNA replication. The shorter protein is also implicated in suppressing RNA silencing-based antiviral defenses. Using a stop codon mutant of Oilseed rape mosaic tobamovirus (ORMV), we demonstrate that the readthrough replicase (p182) is sufficient for gRNA replication and for subgenomic RNA transcription during systemic infection in Nicotiana benthamiana and Arabidopsis thaliana...
November 15, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29138350/the-dead-box-rna-helicase-rh50-is-a-23s-4-5s-rrna-maturation-factor-that-functionally-overlaps-with-the-plastid-signaling-factor-gun1
#13
Francesca Paieri, Luca Tadini, Nikolay Manavski, Tatjana Kleine, Roberto Ferrari, Pietro Angelo Morandini, Paolo Pesaresi, Jörg Meurer, Dario Leister
DEAD-box RNA helicases (DBRHs) modulate RNA secondary structure, allowing RNA molecules to adopt the conformations required for interaction with their target proteins. RH50 is a chloroplast-located DBRH that co-localizes and is co-expressed with GUN1, a central factor in chloroplast-to-nucleus signaling. When combined with mutations that impair plastid gene expression (prors1-1, prpl11-1, prps1-1, prps21-1, prps17-1 and prpl24-1), rh50 and gun1 mutations evoke similar patterns of epistatic effects. These observations, together with the synergistic growth phenotype of the double mutant rh50-1 gun1-102, suggest that RH50 and GUN1 are functionally related and that this function is associated with plastid gene expression, in particular ribosome functioning...
November 14, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29136196/analysis-of-the-natively-unstructured-rna-protein-recognition-core-in-the-escherichia-coli-rna-degradosome-and-its-interactions-with-regulatory-rna-hfq-complexes
#14
Heather A Bruce, Dijun Du, Dijana Matak-Vinkovic, Katarzyna J Bandyra, R William Broadhurst, Esther Martin, Frank Sobott, Alexander V Shkumatov, Ben F Luisi
The RNA degradosome is a multi-enzyme assembly that plays a central role in the RNA metabolism of Escherichia coli and numerous other bacterial species including pathogens. At the core of the assembly is the endoribonuclease RNase E, one of the largest E. coli proteins and also one that bears the greatest region predicted to be natively unstructured. This extensive unstructured region, situated in the C-terminal half of RNase E, is punctuated with conserved short linear motifs that recruit partner proteins, direct RNA interactions, and enable association with the cytoplasmic membrane...
November 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29133145/egfr-and-ras-regulate-ddx59-during-lung-cancer-development
#15
Lin Yang, Hanyin Zhang, Dan Chen, Peikun Ding, Yunchang Yuan, Yandong Zhang
Oncogenes EGFR and ras are frequently mutated and activated in human lung cancers. In this report, we found that both EGFR and Ras signaling can upregulate RNA helicase DDX59 in lung cancer cells. DDX59 can be induced through the mitogen activated protein kinase (MAPK) pathway after EGFR or Ras activation. Inhibitors for Ras/Raf/MAP pathway significantly decreased DDX59 expression at both protein and mRNA levels. Through immunohistochemistry, we found that DDX59 protein expression correlated with Ras and EGFR mutation status in human lung adenocarcinoma...
November 10, 2017: Gene
https://www.readbyqxmd.com/read/29127725/a-loss-of-function-homozygous-mutation-in-ddx59-implicates-a-conserved-dead-box-rna-helicase-in-nervous-system-development-and-function
#16
Vincenzo Salpietro, Stephanie Efthymiou, Andreea Manole, Bhawana Maurya, Sarah Wiethoff, Balasubramaniem Ashokkumar, Maria Concetta Cutrupi, Valeria Dipasquale, Sara Manti, Juan A Botia, Mina Ryten, Jana Vandrovcova, Oscar D Bello, Conceicao Bettencourt, Kshitij Mankad, Ashim Mukherjee, Mousumi Mutsuddi, Henry Houlden
We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with oro-facio-digital syndrome phenotype associated to a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and sub-cortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signalling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies associated genes...
November 11, 2017: Human Mutation
https://www.readbyqxmd.com/read/29123520/dexd-h-box-helicase-36-signaling-via-myeloid-differentiation-primary-response-gene-88-contributes-to-nf-%C3%AE%C2%BAb-activation-to-type-2-porcine-reproductive-and-respiratory-syndrome-virus-infection
#17
Huiyuan Jing, Yanrong Zhou, Liurong Fang, Zhen Ding, Dang Wang, Wenting Ke, Huanchun Chen, Shaobo Xiao
DExD/H-box helicase 36 (DHX36) is known to be an ATP-dependent RNA helicase that unwinds the guanine-quadruplexes DNA or RNA, but emerging data suggest that it also functions as pattern recognition receptor in innate immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide. Interstitial pneumonia is considered to be one of the most obvious clinical signs of PRRSV infection, suggesting that the inflammatory response plays an important role in PRRSV pathogenesis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29118923/ddx3-binding-with-ck1%C3%AE%C2%B5-was-closely-related-to-motor-neuron-degeneration-of-als-by-affecting-neurite-outgrowth
#18
Yanchun Chen, Qing Wang, Qiaozhen Wang, Huancai Liu, Fenghua Zhou, Yawen Zhang, Meng Yuan, Chunyan Zhao, Yingjun Guan, Xin Wang
Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by progressive degeneration of motor neurons. The pathogenesis of ALS remains largely unknown. RNA helicase DDX3 is a multifunctional protein involved in several steps of gene expression. Casein kinase 1ε (CK1ε) is an important signal molecule of Wnt signaling pathway and is closely related to neurite growth. However, the roles of DDX3 and CK1ε in the pathogenesis of ALS remain unclear. In this study, we first investigated the expression of DDX3 and CK1ε in the spinal cord of SOD1-G93A ALS transgenic mice using RT-PCR, Western blot and immunohistochemical technique...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29107693/wdr74-participates-in-an-early-cleavage-of-the-pre-rrna-processing-pathway-in-cooperation-with-the-nucleolar-aaa-atpase-nvl2
#19
Nobuhiro Hiraishi, Yo-Ichi Ishida, Haruka Sudo, Masami Nagahama
WD repeat-containing protein 74 (WDR74), a nucleolar-localized protein, is the mammalian ortholog of Nsa1, a 60S ribosome assembly factor in yeast. We previously showed that WDR74 associates with MTR4, the nuclear exosome-assisting RNA helicase, whose dissociation is prohibited by an ATPase-deficient mutant of the AAA-type chaperone NVL2. However, the functions and regulation of WDR74 during ribosome biogenesis in cooperation with NVL2 remains unknown. Here, we demonstrated that knockdown of WDR74 leads to significant defects in the pre-rRNA cleavage within the internal transcribed spacer 1 (ITS1), occurring in an early stage of the processing pathway...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29107644/the-glycolytic-pyruvate-kinase-is-recruited-directly-into-the-viral-replicase-complex-to-generate-atp-for-rna-synthesis
#20
Chingkai Chuang, K Reddisiva Prasanth, Peter D Nagy
Viruses accomplish their replication by exploiting many cellular resources, including metabolites and energy. Similarly to other (+)RNA viruses, tomato bushy stunt virus (TBSV) induces major changes in infected cells. However, the source of energy required to fuel TBSV replication is unknown. We find that TBSV co-opts the cellular glycolytic ATP-generating pyruvate kinase (PK) directly into the viral replicase complex to boost progeny RNA synthesis. The co-opted PK generates high levels of ATP within the viral replication compartment at the expense of a reduction in cytosolic ATP pools...
November 8, 2017: Cell Host & Microbe
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