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Tamer Sallam, Marius Jones, Brandon J Thomas, Xiaohui Wu, Thomas Gilliland, Kevin Qian, Ascia Eskin, David Casero, Zhengyi Zhang, Jaspreet Sandhu, David Salisbury, Prashant Rajbhandari, Mete Civelek, Cynthia Hong, Ayaka Ito, Xin Liu, Bence Daniel, Aldons J Lusis, Julian Whitelegge, Laszlo Nagy, Antonio Castrillo, Stephen Smale, Peter Tontonoz
Nuclear receptors regulate gene expression in response to environmental cues, but the molecular events governing the cell type specificity of nuclear receptors remain poorly understood. Here we outline a role for a long noncoding RNA (lncRNA) in modulating the cell type-specific actions of liver X receptors (LXRs), sterol-activated nuclear receptors that regulate the expression of genes involved in cholesterol homeostasis and that have been causally linked to the pathogenesis of atherosclerosis. We identify the lncRNA MeXis as an amplifier of LXR-dependent transcription of the gene Abca1, which is critical for regulation of cholesterol efflux...
March 2018: Nature Medicine
David Lemchak, Swati Banerjee, Shaunak S Digambar, Brian L Hood, Thomas P Conrads, Jaroslaw Jedrych, Larisa Geskin, Oleg E Akilov
While mycosis fungoides (MF) is typically an indolent malignancy, it may infrequently undertake an aggressive course. We used proteomic analyses to identify a biomarker of the aggressive course of MF. Results of this investigation demonstrated that PARP-1, heat-shock protein family A (Hsp70) member 1 like (HSAP1L), Hsp70 member 1A (HSPA1A), ATP-depending RNA helicase (DDX17) and the α-isoform of lamina-associated polypeptide 2 (TMPO) had higher expression in aggressive disease versus non-aggressive. Moreover, PARP-1 was overexpressed in patients with early stage of MF who developed later an aggressive disease...
February 2018: Experimental Dermatology
Kai Li, Chunfen Mo, Di Gong, Yan Chen, Zhao Huang, Yanyan Li, Jie Zhang, Lugang Huang, Yuan Li, Frances V Fuller-Pace, Ping Lin, Yuquan Wei
Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective for non-small cell lung cancer (NSCLC) patients with EGFR mutations, almost all these patients will eventually develop acquired resistance to EGFR-TKI. However, the molecular mechanisms responsible for gefitinib resistance remain still not fully understood. Here, we report that elevated DDX17 levels are observed in gefitinib-resistant NSCLC cells than gefitinib-sensitive cells. Upregulation of DDX17 enhances the gefitinib resistance, whereas DDX17-silenced cells partially restore gefitinib sensitivity...
August 1, 2017: Cancer Letters
Bin Lin, Feng Wang, Jiaxiang Wang, Chengyang Xu, Hui Zhao, Zhaoyun Cheng, Deguang Feng
p72 (probable ATP-dependent RNA helicase DDX17) belongs to the DEAD‑box RNA helicase family. p72 is important in RNA processing. Thus, the role of p72 in doxorubicin (DOX)‑induced cardiomyocyte injury was investigated in the present study. The changes in p72 expression levels were studied in cultured neonatal cardiomyocytes and p72 overexpression was induced using adenovirus vectors. To investigate the production of reactive oxygen species (ROS), dihydroethidium staining was conducted. TUNEL and Hoechst staining were used to indicate cell apoptosis...
October 2016: Molecular Medicine Reports
Patrick Connerty, Sarah Bajan, Judit Remenyi, Frances V Fuller-Pace, Gyorgy Hutvagner
MicroRNAs (miRNAs) are short (21-23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors...
October 2016: Biochimica et Biophysica Acta
Pierre L Triozzi, Susan Achberger, Wayne Aldrich, John W Crabb, Yogen Saunthararajah, Arun D Singh
BACKGROUND: Epigenetic events mediated by methylation and histone modifications have been associated with the development of metastasis in patients with uveal melanoma. The role of epigenetic events mediated by microRNA (miR) is less clear. Tumor and plasma miR expression was examined in patients with primary uveal melanoma with tumor monosomy-3, a predictor of metastasis. RESULTS: miR profiling of tumors by microarray found six miRs over-expressed and 19 under-expressed in 33 tumors with monosomy-3 compared to 22 without...
2016: Clinical Epigenetics
Judit Remenyi, Sarah Bajan, Frances V Fuller-Pace, J Simon C Arthur, Gyorgy Hutvagner
miRNAs are small RNAs that are key regulators of gene expression in eukaryotic organisms. The processing of miRNAs is regulated by structural characteristics of the RNA and is also tightly controlled by auxiliary protein factors. Among them, RNA binding proteins play crucial roles to facilitate or inhibit miRNA maturation and can be controlled in a cell, tissue and species-specific manners or in response to environmental stimuli. In this study we dissect the molecular mechanism that promotes the overexpression of miR-132 in mice over its related, co-transcribed and co-regulated miRNA, miR-212...
March 7, 2016: Scientific Reports
Jillian M Emerson, Bradley M Bartholomai, Carol S Ringelberg, Scott E Baker, Jennifer J Loros, Jay C Dunlap
Mutants in the period-1 (prd-1) gene, characterized by a recessive allele, display a reduced growth rate and period lengthening of the developmental cycle controlled by the circadian clock. We refined the genetic location of prd-1 and used whole genome sequencing to find the mutation defining it, confirming the identity of prd-1 by rescuing the mutant circadian phenotype via transformation. PRD-1 is an RNA helicase whose orthologs, DDX5 [DEAD (Asp-Glu-Ala-Asp) Box Helicase 5] and DDX17 in humans and DBP2 (Dead Box Protein 2) in yeast, are implicated in various processes, including transcriptional regulation, elongation, and termination, ribosome biogenesis, and mRNA decay...
December 22, 2015: Proceedings of the National Academy of Sciences of the United States of America
Yu-De Chu, Hsin-Kai Chen, Tao Huang, Shih-Peng Chan
Primary microRNAs (pri-miRNAs) are cleaved by the nuclear RNase III Drosha to produce hairpin-shaped precursor miRNAs (pre-miRNAs). In humans, this process is known to be facilitated by the DEAD-box helicases p68 (DDX5) and p72 (DDX17). In this study, we performed a candidate-based RNAi screen in C. elegans to identify DEAD/H-box proteins involved in miRNA biogenesis. In a let-7(mg279) sensitized genetic background, knockdown of a homolog of yeast splicing factor Prp28p, DDX-23, or a homolog of human helicases p68 and p72, DDX-17, enhanced let-7 loss-of-function phenotypes, suggesting that these helicases play a role in let-7 processing and/or function...
January 15, 2016: Developmental Biology
H Alqahtani, K Gopal, N Gupta, K Jung, A Alshareef, X Ye, F Wu, L Li, R Lai
We have previously demonstrated the existence of two phenotypically distinct cell subsets in estrogen receptor (ER)-positive breast cancer (BC) based on their differential response to a Sox2 reporter (SRR2), with reporter responsive (RR) cells being more tumorigenic and stem-like than reporter unresponsive (RU) cells. To delineate the molecular mechanisms underlying this phenotypic dichotomy, we tested our hypothesis that Sox2, which is a key regulator of the RR phenotype, is under the control of its binding partners...
February 2016: Cellular Signalling
Valerie Le Sage, Alessandro Cinti, Fernando Valiente-Echeverría, Andrew J Mouland
BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) Gag polyprotein is necessary and sufficient to assemble non-infectious particles. Given that HIV-1 subverts many host proteins at all stages of its life cycle, it is essential to identify these interactions as potential targets for antiretroviral therapy. FINDINGS: This work demonstrates the use of proximity-dependent biotin identification (BioID) of host proteins and complexes that are proximal to the N-terminal domains of the HIV-1 Gag polyprotein...
2015: Virology Journal
Nyarie Sithole, Claire Williams, Aisling Vaughan, Andrew Lever
BACKGROUND: HIV/AIDS is the largest global public health problem; about 76 million people have been infected with HIV and 36 million people have already died. Existing antiviral treatment is successful but requires lifelong adherence and mostly targets viral factors. The virus mutates and evades both drugs and the human immune response. Cellular factors are potential therapeutic targets against HIV because the virus must conserve domains that interact with these cellular factors. Unlike many viruses HIV does not encode any helicases but it has been shown to use cellular DDX3...
February 26, 2015: Lancet
Angela Erazo, Stephen P Goff
BACKGROUND: Matrin 3 is a nuclear matrix protein involved in multiple nuclear processes. In HIV-1 infection, Matrin 3 serves as a Rev cofactor important for the cytoplasmic accumulation of HIV-1 transcripts. ZAP is a potent host restriction factor of multiple viruses including retroviruses HIV-1 and MoMuLV. In this study we sought to further characterize Matrin 3 functions in the regulation of HIV gene expression. RESULTS: Here we describe a function for Matrin 3 as a negative regulator of the ZAP-mediated restriction of retroviruses...
2015: Retrovirology
Claire A Williams, Truus E M Abbink, Kuan-Teh Jeang, Andrew M L Lever
Central to the development of new treatments for human immunodeficiency virus 1 (HIV-1) is a more thorough understanding of the viral life cycle and the cellular cofactors upon which this depends. Targeting cellular proteins and their interaction with HIV-1 has the potential to reduce the problem of emerging viral resistance to drugs as mutational escape is more difficult. We performed a short interfering RNA (siRNA) library screen targeting 59 cellular RNA helicases, assessing the effect on both viral capsid protein production and infectious virion formation...
June 2015: Journal of General Virology
Ramiro José González-Duarte, Verna Cázares-Ordoñez, Euclides Ávila-Chávez
MicroRNAs are a class of non-coding RNAs that regulate gene expression at the post-transcriptional level. The major proteins of the canonical microRNA biogenesis pathway in human are: Drosha, DGCR8, DDX5, DDX17, Exportin 5, Dicer and Argonaute 2. Recent studies suggest that gene expression of some canonical microRNA biogenesis components could be regulated by steroid hormones. Furthermore, various alterations in microRNA biogenesis have been associated with diseases like cancer. Due to the importance of microRNAs in cell physiology, the study of the factors that regulate or affect their biogenesis is critical...
September 2014: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
Christine Xing'er Koo, Kouji Kobiyama, Yu J Shen, Nina LeBert, Shandar Ahmad, Muznah Khatoo, Taiki Aoshi, Stephan Gasser, Ken J Ishii
RNA:DNA hybrids form in the nuclei and mitochondria of cells as transcription-induced R-loops or G-quadruplexes, but exist only in the cytosol of virus-infected cells. Little is known about the existence of RNA:DNA hybrids in the cytosol of virus-free cells, in particular cancer or transformed cells. Here, we show that cytosolic RNA:DNA hybrids are present in various human cell lines, including transformed cells. Inhibition of RNA polymerase III (Pol III), but not DNA polymerase, abrogated cytosolic RNA:DNA hybrids...
March 20, 2015: Journal of Biological Chemistry
Ryan H Moy, Sara Cherry
No abstract text is available yet for this article.
2014: Cell Cycle
Ryan H Moy, Brian S Cole, Ari Yasunaga, Beth Gold, Ganesh Shankarling, Andrew Varble, Jerome M Molleston, Benjamin R tenOever, Kristen W Lynch, Sara Cherry
DEAD-box helicases play essential roles in RNA metabolism across species, but emerging data suggest that they have additional functions in immunity. Through RNAi screening, we identify an evolutionarily conserved and interferon-independent role for the DEAD-box helicase DDX17 in restricting Rift Valley fever virus (RVFV), a mosquito-transmitted virus in the bunyavirus family that causes severe morbidity and mortality in humans and livestock. Loss of Drosophila DDX17 (Rm62) in cells and flies enhanced RVFV infection...
August 14, 2014: Cell
S Zaccara, T Tebaldi, C Pederiva, Y Ciribilli, A Bisio, A Inga
The increasing number of genome-wide transcriptome analyses focusing on p53-induced cellular responses in many cellular contexts keeps adding to the already numerous p53-regulated transcriptional networks. To investigate post-transcriptional controls as an additional dimension of p53-directed gene expression responses, we performed a translatome analysis through polysomal profiling on MCF7 cells upon 16 hours of doxorubicin or nutlin-3a treatment. The comparison between the transcriptome and the translatome revealed a considerable level of uncoupling, characterized by genes whose transcription variations did not correlate with translation variations...
October 2014: Cell Death and Differentiation
Etienne Dardenne, Micaela Polay Espinoza, Laurent Fattet, Sophie Germann, Marie-Pierre Lambert, Helen Neil, Eleonora Zonta, Hussein Mortada, Lise Gratadou, Mathieu Deygas, Fatima Zahra Chakrama, Samaan Samaan, François-Olivier Desmet, Léon-Charles Tranchevent, Martin Dutertre, Ruth Rimokh, Cyril F Bourgeois, Didier Auboeuf
The RNA helicases DDX5 and DDX17 are members of a large family of highly conserved proteins that are involved in gene-expression regulation; however, their in vivo targets and activities in biological processes such as cell differentiation, which requires reprogramming of gene-expression programs at multiple levels, are not well characterized. Here, we uncovered a mechanism by which DDX5 and DDX17 cooperate with heterogeneous nuclear ribonucleoprotein (hnRNP) H/F splicing factors to define epithelial- and myoblast-specific splicing subprograms...
June 26, 2014: Cell Reports
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