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Rna Interactions

Helga B Landsverk, Lise E Sandquist, Sreerama C Sridhara, Gro Elise Rødland, João C Sabino, Sérgio F de Almeida, Beata Grallert, Laura Trinkle-Mulcahy, Randi G Syljuåsen
Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is a key factor activated by DNA damage and replication stress. An alternative pathway for ATR activation has been proposed to occur via stalled RNA polymerase II (RNAPII). However, how RNAPII might signal to activate ATR remains unknown. Here, we show that ATR signaling is increased after depletion of the RNAPII phosphatase PNUTS-PP1, which dephosphorylates RNAPII in its carboxy-terminal domain (CTD). High ATR signaling was observed in the absence and presence of ionizing radiation, replication stress and even in G1, but did not correlate with DNA damage or RPA chromatin loading...
December 12, 2018: Nucleic Acids Research
S Saif Hasan, Chengqun Sun, Arthur S Kim, Yasunori Watanabe, Chun-Liang Chen, Thomas Klose, Geeta Buda, Max Crispin, Michael S Diamond, William B Klimstra, Michael G Rossmann
Alphaviruses are enveloped pathogens that cause arthritis and encephalitis. Here, we report a 4.4-Å cryoelectron microscopy (cryo-EM) structure of eastern equine encephalitis virus (EEEV), an alphavirus that causes fatal encephalitis in humans. Our analysis provides insights into viral entry into host cells. The envelope protein E2 showed a binding site for the cellular attachment factor heparan sulfate. The presence of a cryptic E2 glycan suggests how EEEV escapes surveillance by lectin-expressing myeloid lineage cells, which are sentinels of the immune system...
December 11, 2018: Cell Reports
Elisabeth R Knoll, Z Iris Zhu, Debasish Sarkar, David Landsman, Randall H Morse
The Mediator complex stimulates the cooperative assembly of a pre-initiation complex (PIC) and recruitment of RNA Polymerase II (Pol II) for gene activation. The core Mediator complex is organized into head, middle, and tail modules, and in budding yeast ( Saccharomyces cerevisiae ), Mediator recruitment has generally been ascribed to sequence-specific activators engaging the tail module triad of Med2-Med3-Med15 at upstream activating sequences (UASs). We show that yeast lacking Med2-Med3-Med15 are viable and that Mediator and PolII are recruited to promoters genome-wide in these cells, albeit at reduced levels...
December 12, 2018: ELife
Xiao-Qin Zhang, Jian-Hua Yang
Over 100 types of chemical modifications have been identified in protein-coding and noncoding RNAs (ncRNAs). However, the prevalence, regulation, and function of diverse RNA modifications remain largely unknown. In this chapter, we describe how to annotate, visualize, and analyze the RNA modification sites from the high-throughput epitranscriptome sequencing data using RMBase platform and software. We developed two stand-alone computational software, modAnnotator and metaProfile, to annotate and visualize RNA modification sites and their prevalence in the gene body...
2019: Methods in Molecular Biology
Stefan C Weise, Ganeshkumar Arumugam, Alejandro Villarreal, Pavankumar Videm, Stefanie Heidrich, Nils Nebel, Verónica I Dumit, Farahnaz Sananbenesi, Viktoria Reimann, Madeline Craske, Oliver Schilling, Wolfgang R Hess, Andre Fischer, Rolf Backofen, Tanja Vogel
Rett syndrome is a complex neurodevelopmental disorder that is mainly caused by mutations in MECP2. However, mutations in FOXG1 cause a less frequent form of atypical Rett syndrome, called FOXG1 syndrome. FOXG1 is a key transcription factor crucial for forebrain development, where it maintains the balance between progenitor proliferation and neuronal differentiation. Using genome-wide small RNA sequencing and quantitative proteomics, we identified that FOXG1 affects the biogenesis of miR200b/a/429 and interacts with the ATP-dependent RNA helicase, DDX5/p68...
December 11, 2018: Molecular Neurobiology
Yong Zhou, Chengzhi Gu, Jia Li, Lianhai Zhu, Guoxiang Huang, Jie Dai, Huaiyu Huang
Purpose: Parkinson's disease (PD) is a common neurodegenerative movement disorder, but the pathogenesis remains elusive. This study was aimed to explore key genes and long noncoding RNAs (lncRNAs) associated with PD. Materials and methods: Three patients with PD and three normal controls were enrolled in the present study from July 12, 2017, to August 29, 2017. RNA sequencing and bioinformatics analysis were performed to obtain differentially expressed micro RNAs (DEmRNAs) and lncRNAs (DElncRNAs) between patients with PD and normal controls...
2018: Neuropsychiatric Disease and Treatment
Gabriela Paroni, Marco Bolis, Adriana Zanetti, Paolo Ubezio, Kristian Helin, Peter Staller, Lars Ole Gerlach, Maddalena Fratelli, Richard M Neve, Mineko Terao, Enrico Garattini
Targeting of histone methylation has therapeutic potential in oncology. Here, we provide proof-of-principle that pharmacological inhibition of KDM5 histone-demethylases is a new strategy for the personalized treatment of HER2+ breast cancer. The anti-proliferative effects of the prototype of a new class of selective KDM5-inhibitors (KDM5-inh1) are evaluated in 40 cell lines, recapitulating the heterogeneity of breast cancer. This analysis demonstrates that HER2+ cells are particularly sensitive to KDM5 inhibition...
December 11, 2018: Oncogene
Eshwar R Tammineni, Elba D Carrillo, Rubén Soto-Acosta, Antonio H Angel-Ambrocio, María C García, Patricia Bautista-Carbajal, Rosa M Del Angel, Jorge A Sánchez
The auxiliary β4 subunit of the cardiac Cav 1.2 channel plays a poorly understood role in gene transcription. Here, we characterized the regulatory effects of the β4 subunit in H9c2 rat cardiac cells on the abundances of Ifnb mRNA [which encodes interferon-β (IFN-β)] and of the IFN-β-related genes Ddx58 , Ifitm3 , Irf7 , Stat2 , Ifih1 , and Mx1 , as well as on the abundances of the antiviral proteins DDX58, IRF7, STAT2, and IFITM3. Knocking down the β4 subunit in H9c2 cells reduced the expression of IFN-β-stimulated genes...
December 11, 2018: Science Signaling
Nooshin Movahed, Jiaqi Sun, Hojatollah Vali, Jean-Francois Laliberte, Huanquan Zheng
Like other positive-strand RNA viruses, Turnip mosaic virus (TuMV) infection leads to the formation of viral vesicles at the endoplasmic reticulum (ER). Once released from the ER, the viral vesicles mature intracellularly and then move intercellularly. While it is known that the membrane-associated viral protein 6K2 plays a role in the process, the contribution of host proteins is poorly defined. Here, we show that 6K2 interacts with RHD3, an ER fusogen required for efficient ER fusion. When RHD3 is mutated, a delay in the development of TuMV infection is observed...
December 11, 2018: Plant Physiology
Alan L Jiao, Roberto Perales, Neil T Umbreit, Jeffrey R Haswell, Mary E Piper, Brian D Adams, David Pellman, Scott Kennedy, Frank J Slack
The accurate inheritance of genetic material is a basic necessity in all domains of life and an unexpectedly large number of RNA processing factors are required for mitotic progression and genome stability. NRDE2 (nuclear RNAi defective-2) is an evolutionarily conserved protein originally discovered for its role in nuclear RNA interference (RNAi) and heritable gene silencing in Caenorhabditis elegans (C. elegans). The function of the human NRDE2 gene remains poorly understood. Here we show that human NRDE2 is an essential protein required for suppressing intron retention in a subset of pre-mRNAs containing short, GC-rich introns with relatively weak 5' and 3' splice sites...
December 11, 2018: RNA
Abigail F Groff, A Rasim Barutcu, Jordan P Lewandowski, John L Rinn
BACKGROUND: Recently, it has become clear that some promoters function as long-range regulators of gene expression. However, direct and quantitative assessment of enhancer activity at long intergenic noncoding RNA (lincRNA) or mRNA gene bodies has not been performed. To unbiasedly assess the enhancer capacity across lincRNA and mRNA loci, we performed a massively parallel reporter assay (MPRA) on six lincRNA loci and their closest protein-coding neighbors. RESULTS: For both gene classes, we find significantly more MPRA activity in promoter regions than in gene bodies...
December 11, 2018: Genome Biology
Xiuyuan Li, Zenglei Zhang, Hua Jiang, Qiang Li, Ruliang Wang, Hongliang Pan, Yingying Niu, Fenghai Liu, Hongmei Gu, Xingjun Fan, Jinxia Gao
BACKGROUND/AIMS: Circular RNAs (circRNAs) are key regulators in the development and progression of human cancers, however its role in non-small cell lung cancer (NSCLC) tumorigenesis is not well understood. The aim of this study is to identify the expression level of circPVT1 in NSCLC and further investigated its functional relevance with NSCLC progression both in vitro and in vivo. METHODS: Quantative real-time PCR was used for the measurement of circPVT1 in NSCLC specimens and cell lines...
2018: Cellular Physiology and Biochemistry
Yi-Ting Sun, Matthew D Shortridge, Gabriele Varani
The RRM (RNA-recognition motif), the most abundant RNA-binding motif in eukaryotes, is a small folded domain of about 90 amino acids, yet the β2-β3 hairpin corresponding to strands 2 and 3 of the β-sheet, and the intervening loop makes essential interactions with RNA in many RRM complexes. We designed a series of small cyclic peptides mimics of the β2-β3 hairpin of Rbfox2 protein, that recognize the terminal loop of precursor miR-20b, to investigate whether it is possible to mimic the full RNA-binding protein with a minimal structurally pre-organized peptide...
December 11, 2018: Chembiochem: a European Journal of Chemical Biology
Vimala Parihar, Deepshikha Arya, Akanksha Walia, Vidhi Tyagi, Meenakshi Dangwal, Vibha Verma, Ridhi Khurana, Neelima Boora, Sanjay Kapoor, Meenu Kapoor
In flowering plants LIKE HETEROCHROMATIN PROTEIN 1 (LHP1)/TERMINAL FLOWER 2 (TFL2) is known to interact with polycomb group (PcG) and non-PcG proteins and control developmental programs. LHP1/TFL2 is an ancient protein and has been characterized in the early-divergent plant Physcomitrella patens. However, interacting partners of PpLHP1 other than the chromomethylase PpCMT have not been identified to date. Also, while a functional Polycomb Repressive Complex 2 (PRC2) is known to exist in P. patens, there are no experimental evidences to support existence of PRC1-like complexes in these mosses...
December 7, 2018: Plant Journal: for Cell and Molecular Biology
Rasoul Abdollahzadeh, Abdolreza Daraei, Yaser Mansoori, Masoumeh Sepahvand, Mahsa M Amoli, Javad Tavakkoly-Bazzaz
Breast cancer (BC) is the most frequently occurring malignancy in women worldwide. Despite the substantial advancement in understanding the molecular mechanisms and management of BC, it remains the leading cause of cancer death in women. One of the main reasons for this obstacle is that we have not been able to find the Achilles heel for the BC as a highly heterogeneous disease. Accumulating evidence has revealed that noncoding RNAs (ncRNAs), play key roles in the development of BC; however, the involving of complex regulatory interactions between the different varieties of ncRNAs in the development of this cancer has been poorly understood...
December 10, 2018: Journal of Cellular Physiology
Liman Qiu, Yanbing Huang, Zhenli Li, Xiuqing Dong, Geng Chen, Haipo Xu, Yongyi Zeng, Zhixiong Cai, Xiaolong Liu, Jingfeng Liu
Circular RNAs (circRNAs) can participate in various biological processes, including tumorigenesis, through their microRNA response elements (MREs). Alterations in circRNA profiles during hepatocellular carcinoma (HCC) progression and the clinical significance thereof remain unclear. Here, we present extensive analysis of circRNA profiles in tumor and matched peritumor tissues collected from 10 HCC patients, conducted to identify circRNAs related to HCC progression. A total of 42 dysregulated circRNAs (38 down-regulated and 4 up-regulated) were identified in HCC tumor tissues when compared with matched peritumor tissues, revealing the heterogeneity of circRNA profiles in HCC...
December 8, 2018: Molecular Oncology
Julien J Karrich, Mónica Romera-Hernández, Natalie Papazian, Sharon Veenbergen, Ferry Cornelissen, Patricia Aparicio-Domingo, Frances H Stenhouse, C Diana Peddie, Remco M Hoogenboezem, Chelsea W J den Hollander, Terri Gaskell, Tanya Medley, Louis Boon, C Claire Blackburn, David R Withers, Janneke N Samsom, Tom Cupedo
Under homeostatic conditions, dendritic cells (DCs) continuously patrol the intestinal lamina propria. Upon antigen encounter, DCs initiate C-C motif chemokine receptor 7 (CCR7) expression and migrate into lymph nodes to direct T cell activation and differentiation. The mechanistic underpinnings of DC migration from the tissues to lymph nodes have been largely elucidated, contributing greatly to our understanding of DC functionality and intestinal immunity. In contrast, the molecular mechanisms allowing DCs to efficiently migrate through the complex extracellular matrix of the intestinal lamina propria prior to antigen encounter are still incompletely understood...
December 7, 2018: European Journal of Immunology
Daria Esyunina, Danil Pupov, Andrey Kulbachinskiy
Bacterial RNA polymerase (RNAP) serves as a primase during replication of single-stranded plasmids and filamentous phages. Primer RNA (prRNA) synthesis from the origin regions of these replicons depends on the σ factor that normally participates in promoter recognition. However, it was proposed that σ may not be required for origin recognition but is rather involved in RNA extension by RNAP. Here, by analyzing the natural replication origin of bacteriophage M13 and synthetic single-stranded DNA (ssDNA) templates, we show that interactions of σ with promoter-like motifs stabilize priming complexes and can control prRNA synthesis by trapping RNAP on the template...
December 8, 2018: FEBS Letters
Chao Song, Yunhe Xiong, Wenbiao Liao, Lingchao Meng, Sixing Yang
Long noncoding RNA (lncRNA) exerts an essential role in the pathological processes of many diseases. Our previous study found that lncRNA ATB was highly expressed in renal cell carcinoma (RCC). Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and migration-related assays were conducted to access the regulatory effects of lncRNA ATB on proliferative and migratory capacities of RCC cells. Flow cytometry was carried out to determine cell cycle and apoptosis influenced by lncRNA ATB. The interaction among lncRNA ATB, DNMT1, and p53 was evaluated through RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and western blot analyses...
December 8, 2018: Journal of Cellular Physiology
Gan-Xun Li, Ze-Yang Ding, Yu-Wei Wang, Tong-Tong Liu, Wei-Xun Chen, Jing-Jing Wu, Wei-Qi Xu, Peng Zhu, Bi-Xiang Zhang
DNA methylation is a crucial regulator of gene transcription in the etiology and pathogenesis of hepatocellular carcinoma (HCC). Thus, it is reasonable to identify DNA methylation-related prognostic markers. Currently, we aimed to make an integrative epigenetic analysis of HCC to identify the effectiveness of epigenetic drivers in predicting prognosis for HCC patients. By the software pipeline TCGA-Assembler 2, RNA-seq, and methylation data were downloaded and processed from The Cancer Genome Atlas. A bioconductor package MethylMix was utilized to incorporate gene expression and methylation data on all 363 samples and identify 589 epigenetic drivers with transcriptionally predictive...
December 7, 2018: Journal of Cellular Physiology
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