Large-Scale Analysis of Genome and Transcriptome Alterations in Multiple Tumors Unveils Novel Cancer-Relevant Splicing Networks
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RBM11 Sirna (H): Sc-91387
SANTA CRUZ BIOTECHNOLOGY, INC. RBM11 siRNA (h): sc-91387 BACKGROUND PRODUCT Proteins containing RNA recognition motifs, including various hnRNP proteins, RBM11 siRNA (h) is a pool of 3 target-specific 19-25 nt siRNAs designed are implicated in the regulation of alternative splicing and protein components to knock down gene expression. Each vial contains 3.3 nmol of lyophilized of snRNPs. The RBM (RNA-binding motif) gene family encodes proteins with siRNA, sufficient for a 10 µM solution once resuspended using protocol an RNA binding motif that have been suggested to play a role in the modu- below. Suitable for 50-100 transfections. Also see RBM11 shRNA Plasmid (h): lation of apoptosis. RBM11 (RNA-binding protein 11) is a 281 amino acid sc-91387-SH and RBM11 shRNA (h) Lentiviral Particles: sc-91387-V as alter- nuclear protein that contains one RNA recognition motif. RBM11 exists as nate gene silencing products. two isoforms produced by alternative splicing and is expressed in testis, kid- For independent verification of RBM11 (h) gene silencing results, we also ney, spleen, brain, spinal cord and mammary gland. The gene that encodes provide the individual siRNA duplex components. Each is available as 3.3 nmol RBM11 maps to chromosome 21, the smallest of the human chromosomes. of lyophilized siRNA. These include: sc-91387A, sc-91387B and sc-91387C. Down syndrome, also known as trisomy 21, is the disease most commonly associated with chromosome 21. Alzheimer’s disease, Jervell and Lange- STORAGE AND RESUSPENSION Nielsen syndrome and amyotrophic lateral sclerosis are also associated with chromosome 21. Store lyophilized siRNA duplex at -20° C with desiccant. -
Sanjay Kumar Gupta
The human CCHC-type Zinc Finger Nucleic Acid Binding Protein (CNBP) binds to the G-rich elements in target mRNA coding sequences and promotes translation Das humane CCHC-Typ-Zinkfinger-Nukleinsäure-Binde-Protein (CNBP) bindet an G-reiche Elemente in der kodierenden Sequenz seiner Ziel-mRNAs und fördert deren Translation Doctoral thesis for a doctoral degree at the Graduate School of Life Sciences, Julius-Maximilians-Universität WürzBurg, Section: Biomedicine suBmitted By Sanjay Kumar Gupta from Varanasi, India WürzBurg, 2016 1 Submitted on: …………………………………………………………..…….. Office stamp Members of the Promotionskomitee: Chairperson: Prof. Dr. Alexander Buchberger Primary Supervisor: Dr. Stefan Juranek Supervisor (Second): Prof. Dr. Utz Fischer Supervisor (Third): Dr. Markus Landthaler Date of Public Defence: …………………………………………….………… Date of Receipt of Certificates: ………………………………………………. 2 Summary The genetic information encoded with in the genes are transcribed and translated to give rise to the functional proteins, which are building block of a cell. At first, it was thought that the regulation of gene expression particularly occurs at the level of transcription By various transcription factors. Recent discoveries have shown the vital role of gene regulation at the level of RNA also known as post-transcriptional gene regulation (PTGR). Apart from non-coding RNAs e.g. micro RNAs, various RNA Binding proteins (RBPs) play essential role in PTGR. RBPs have been implicated in different stages of mRNA life cycle ranging from splicing, processing, transport, localization and decay. In last 20 years studies have shown the presence of hundreds of RBPs across eukaryotic systems many of which are widely conserved. Given the rising numBer of RBPs and their link to human diseases it is quite evident that RBPs have major role in cellular processes and their regulation. -
ZCCHC8, the Nuclear Exosome Targeting Component, Is Mutated in Familial Pulmonary Fibrosis and Is Required for Telomerase RNA Maturation
Downloaded from genesdev.cshlp.org on October 7, 2021 - Published by Cold Spring Harbor Laboratory Press ZCCHC8, the nuclear exosome targeting component, is mutated in familial pulmonary fibrosis and is required for telomerase RNA maturation Dustin L. Gable,1,2,3 Valeriya Gaysinskaya,2,3 Christine C. Atik,2,3 C. Conover Talbot Jr.,4 Byunghak Kang,5 Susan E. Stanley,1,2,3 Elizabeth W. Pugh,6 Nuria Amat-Codina,2,3 Kara M. Schenk,7 Murat O. Arcasoy,8 Cory Brayton,5 Liliana Florea,6 and Mary Armanios2,3,6,9,10 1Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; 2Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA; 3Telomere Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA; 4Institute for Basic Biomedical Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; 5Department of Comparative and Molecular Pathobiology, 6Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA; 7Osler Medical Housestaff Training Program, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA; 8Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27708, USA; 9Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA Short telomere syndromes manifest as familial idiopathic pulmonary fibrosis; they are the most common premature aging disorders. We used genome-wide linkage to identify heterozygous loss of function of ZCCHC8, a zinc-knuckle containing protein, as a cause of autosomal dominant pulmonary fibrosis. ZCCHC8 associated with TR and was required for telomerase function. -
Overlap of Quantitative Trait Loci for Early Growth Rate, and for Body
REPRODUCTIONRESEARCH Functional reconstruction of NANOS3 expression in the germ cell lineage by a novel transgenic reporter reveals distinct subcellular localizations of NANOS3 Masashi Yamaji1, Takashi Tanaka2, Mayo Shigeta1, Shinichiro Chuma2, Yumiko Saga3 and Mitinori Saitou1,4,5 1Laboratory for Mammalian Germ Cell Biology, RIKEN Center for Developmental Biology, 2-2-3 Minatojima- Minamimachi, Chuo-ku, Kobe 650-0047, Japan, 2Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan, 3Department of Genetics and Division of Mammalian Development, National Institute of Genetics, SOKENDAI, 1111 Yata, Mishima, Shizuoka 411-8540, Japan, 4Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida- Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan and 5JST, CREST, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan Correspondence should be addressed to M Saitou at Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University; Email: [email protected] Abstract Mutations of RNA-binding proteins such as NANOS3, TIAL1, and DND1 in mice have been known to result in the failure of survival and/or proliferation of primordial germ cells (PGCs) soon after their fate is specified (around embryonic day (E) 8.0), leading to the infertility of these animals. However, the mechanisms of actions of these RNA-binding proteins remain largely unresolved. As a foundation to explore the role of these RNA-binding proteins in germ cells, we established a novel transgenic reporter strain that expresses NANOS3 fused with EGFP under the control of Nanos3 regulatory elements. NANOS3–EGFP exhibited exclusive expression in PGCs as early as E7.25, and continued to be expressed in female germ cells until around E14.5 and in male germ cells throughout the fetal period with declining expression levels after E16.5. -
1213508110.Full.Pdf
Staufen2 functions in Staufen1-mediated mRNA decay INAUGURAL ARTICLE by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity Eonyoung Parka,b, Michael L. Gleghorna,b, and Lynne E. Maquata,b,1 aDepartment of Biochemistry and Biophysics, School of Medicine and Dentistry, and bCenter for RNA Biology, University of Rochester, Rochester, NY 14642 This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2011. Edited by Michael R. Botchan, University of California, Berkeley, CA, and approved November 16, 2012 (received for review August 3, 2012) Staufen (STAU)1-mediated mRNA decay (SMD) is a posttranscrip- harbor a STAU1-binding site (SBS) downstream of their normal tional regulatory mechanism in mammals that degrades mRNAs termination codon in a pathway called STAU1-mediated mRNA harboring a STAU1-binding site (SBS) in their 3′-untranslated regions decay or SMD (13, 14), and work published by others indicates (3′ UTRs). We show that SMD involves not only STAU1 but also its that SMD does not involve STAU2 (3, 15). paralog STAU2. STAU2, like STAU1, is a double-stranded RNA-binding According to our current model for SMD, when translation protein that interacts directly with the ATP-dependent RNA helicase terminates upstream of an SBS, recruitment of the nonsense-me- diated mRNA decay (NMD) factor UPF1 to SBS-bound STAU1 up-frameshift 1 (UPF1) to reduce the half-life of SMD targets that form fl an SBS by either intramolecular or intermolecular base-pairing. Com- triggers mRNA decay. SMD in uences a number of cellular pro- pared with STAU1, STAU2 binds ∼10-foldmoreUPF1and∼two- to cesses, including the differentiation of mouse C2C12 myoblasts to myotubes (16), the motility of human HaCaT keratinocytes (17), fivefold more of those SBS-containing mRNAs that were tested, and it and the differentiation of mouse 3T3-L1 preadipocytes to adipo- comparably promotes UPF1 helicase activity, which is critical for SMD. -
Downloaded from the TCGA Data Portal ( Data.Nci.Nih.Gov/Tcga/) (Supplemental Table S1)
bioRxiv preprint doi: https://doi.org/10.1101/023010; this version posted February 11, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Large-scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer-relevant splicing networks Endre Sebestyén1,*, Babita Singh1,*, Belén Miñana1,2, Amadís Pagès1, Francesca Mateo3, Miguel Angel Pujana3, Juan Valcárcel1,2,4, Eduardo Eyras1,4,5 1Universitat Pompeu Fabra, Dr. Aiguader 88, E08003 Barcelona, Spain 2Centre for Genomic Regulation, Dr. Aiguader 88, E08003 Barcelona, Spain 3Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), E08908 L’Hospitalet del Llobregat, Spain. 4Catalan Institution for Research and Advanced Studies, Passeig Lluís Companys 23, E08010 Barcelona, Spain *Equal contribution 5Correspondence to: [email protected] Keywords: alternative splicing, RNA binding proteins, splicing networks, cancer 1 bioRxiv preprint doi: https://doi.org/10.1101/023010; this version posted February 11, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Abstract Alternative splicing is regulated by multiple RNA-binding proteins and influences the expression of most eukaryotic genes. However, the role of this process in human disease, and particularly in cancer, is only starting to be unveiled. -
Immunoprecipitation and Mass Spectrometry Defines an Extensive
BRES : 44759 Model7 pp: À 1221ðcol:fig: : NILÞ brain research ] ( ]]]]) ]]]– ]]] Available online at www.sciencedirect.com 121 122 123 124 125 126 www.elsevier.com/locate/brainres 127 128 129 Review 130 131 fi 132 Immunoprecipitation and mass spectrometry de nes 133 – 134 an extensive RBM45 protein protein interaction 135 Q2 136 network 137 138 a a,b a a c 139 Yang Li , Mahlon Collins , Jiyan An , Rachel Geiser , Tony Tegeler , c c c a,b,n 140 Q1 Kristine Tsantilas , Krystine Garcia , Patrick Pirrotte , Robert Bowser 141 aDivisions of Neurology and Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 142 Phoenix, AZ 85013, USA 143 bUniversity of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA 144 cCenter for Proteomics, TGen (Translational Genomics Research Institute), Phoenix, AZ 85004, USA 145 146 147 article info abstract 148 149 Article history: The pathological accumulation of RNA-binding proteins (RBPs) within inclusion bodies is a 150 Received 30 January 2016 hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration 151 Received in revised form (FTLD). RBP aggregation results in both toxic gain and loss of normal function. Determining 152 25 February 2016 the protein binding partners and normal functions of disease-associated RBPs is necessary 153 Accepted 28 February 2016 to fully understand molecular mechanisms of RBPs in disease. Herein, we characterized 154 the protein–protein interactions (PPIs) of RBM45, a RBP that localizes to inclusions in ALS/ 155 – fi Keywords: FTLD. Using immunoprecipitation coupled to mass spectrometry (IP MS), we identi ed 132 156 fi RBM45 proteins that speci cally interact with RBM45 within HEK293 cells. -
A SARS-Cov-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing Supplementary Information Supplementary Discussion All SARS-CoV-2 protein and gene functions described in the subnetwork appendices, including the text below and the text found in the individual bait subnetworks, are based on the functions of homologous genes from other coronavirus species. These are mainly from SARS-CoV and MERS-CoV, but when available and applicable other related viruses were used to provide insight into function. The SARS-CoV-2 proteins and genes listed here were designed and researched based on the gene alignments provided by Chan et. al. 1 2020 . Though we are reasonably sure the genes here are well annotated, we want to note that not every protein has been verified to be expressed or functional during SARS-CoV-2 infections, either in vitro or in vivo. In an effort to be as comprehensive and transparent as possible, we are reporting the sub-networks of these functionally unverified proteins along with the other SARS-CoV-2 proteins. In such cases, we have made notes within the text below, and on the corresponding subnetwork figures, and would advise that more caution be taken when examining these proteins and their molecular interactions. Due to practical limits in our sample preparation and data collection process, we were unable to generate data for proteins corresponding to Nsp3, Orf7b, and Nsp16. Therefore these three genes have been left out of the following literature review of the SARS-CoV-2 proteins and the protein-protein interactions (PPIs) identified in this study. -
A Comprehensive Analysis of 3' End Sequencing Data Sets Reveals Novel
bioRxiv preprint doi: https://doi.org/10.1101/033001; this version posted November 26, 2015. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. A comprehensive analysis of 3’ end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogenous ribonucleoprotein C on cleavage and polyadenylation 1 1 1 1 1 Andreas J. Gruber , Ralf Schmidt , Andreas R. Gruber , Georges Martin , Souvik Ghosh , 1,2 1 1,§ Manuel Belmadani , Walter Keller , Mihaela Zavolan 1 Computational and Systems Biology, Biozentrum, University of Basel, Klingelbergstrasse 5070, 4056 Basel, Switzerland 2 Current address: University of British Columbia, 177 Michael Smith Laboratories, 2185 East Mall Vancouver BC V6T 1Z4 § To whom correspondence should be addressed ([email protected]) Abstract Alternative polyadenylation (APA) is a general mechanism of transcript diversification in mammals, which has been recently linked to proliferative states and cancer. Different 3’ untranslated region (3’ UTR) isoforms interact with different RNA binding proteins (RBPs), which modify the stability, translation, and subcellular localization of the corresponding transcripts. Although the heterogeneity of premRNA 3’ end processing has been established with highthroughput approaches, the mechanisms that underlie systematic changes in 3’ UTR lengths remain to be characterized. Through a uniform analysis of a large number of 3’ end sequencing data sets we have uncovered 18 signals, 6 of which novel, whose positioning with respect to premRNA cleavage sites indicates a role in premRNA 3’ end processing in both mouse and human. -
Genetic Variant in 3' Untranslated Region of the Mouse Pycard Gene
bioRxiv preprint doi: https://doi.org/10.1101/2021.03.26.437184; this version posted March 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 2 3 Title: 4 Genetic Variant in 3’ Untranslated Region of the Mouse Pycard Gene Regulates Inflammasome 5 Activity 6 Running Title: 7 3’UTR SNP in Pycard regulates inflammasome activity 8 Authors: 9 Brian Ritchey1*, Qimin Hai1*, Juying Han1, John Barnard2, Jonathan D. Smith1,3 10 1Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 11 Cleveland, OH 44195 12 2Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 13 44195 14 3Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western 15 Reserve University, Cleveland, OH 44195 16 *, These authors contributed equally to this study. 17 Address correspondence to Jonathan D. Smith: email [email protected]; ORCID ID 0000-0002-0415-386X; 18 mailing address: Cleveland Clinic, Box NC-10, 9500 Euclid Avenue, Cleveland, OH 44195, USA. 19 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.03.26.437184; this version posted March 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 20 Abstract 21 Quantitative trait locus mapping for interleukin-1 release after inflammasome priming and activation 22 was performed on bone marrow-derived macrophages (BMDM) from an AKRxDBA/2 strain intercross. -
Comparative Interactomics Analysis of Different ALS-Associated Proteins
Acta Neuropathol (2016) 132:175–196 DOI 10.1007/s00401-016-1575-8 ORIGINAL PAPER Comparative interactomics analysis of different ALS‑associated proteins identifies converging molecular pathways Anna M. Blokhuis1 · Max Koppers1,2 · Ewout J. N. Groen1,2,9 · Dianne M. A. van den Heuvel1 · Stefano Dini Modigliani4 · Jasper J. Anink5,6 · Katsumi Fumoto1,10 · Femke van Diggelen1 · Anne Snelting1 · Peter Sodaar2 · Bert M. Verheijen1,2 · Jeroen A. A. Demmers7 · Jan H. Veldink2 · Eleonora Aronica5,6 · Irene Bozzoni3 · Jeroen den Hertog8 · Leonard H. van den Berg2 · R. Jeroen Pasterkamp1 Received: 22 January 2016 / Revised: 14 April 2016 / Accepted: 15 April 2016 / Published online: 10 May 2016 © The Author(s) 2016. This article is published with open access at Springerlink.com Abstract Amyotrophic lateral sclerosis (ALS) is a dev- OPTN and UBQLN2, in which mutations caused loss or astating neurological disease with no effective treatment gain of protein interactions. Several of the identified inter- available. An increasing number of genetic causes of ALS actomes showed a high degree of overlap: shared binding are being identified, but how these genetic defects lead to partners of ATXN2, FUS and TDP-43 had roles in RNA motor neuron degeneration and to which extent they affect metabolism; OPTN- and UBQLN2-interacting proteins common cellular pathways remains incompletely under- were related to protein degradation and protein transport, stood. To address these questions, we performed an inter- and C9orf72 interactors function in mitochondria. To con- actomic analysis to identify binding partners of wild-type firm that this overlap is important for ALS pathogenesis, (WT) and ALS-associated mutant versions of ATXN2, we studied fragile X mental retardation protein (FMRP), C9orf72, FUS, OPTN, TDP-43 and UBQLN2 in neuronal one of the common interactors of ATXN2, FUS and TDP- cells. -
Mouse Rbm7 Conditional Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Rbm7 Conditional Knockout Project (CRISPR/Cas9) Objective: To create a Rbm7 conditional knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Rbm7 gene (NCBI Reference Sequence: NM_144948 ; Ensembl: ENSMUSG00000042396 ) is located on Mouse chromosome 9. 5 exons are identified, with the ATG start codon in exon 1 and the TAA stop codon in exon 5 (Transcript: ENSMUST00000170000). Exon 4 will be selected as conditional knockout region (cKO region). Deletion of this region should result in the loss of function of the Mouse Rbm7 gene. To engineer the targeting vector, homologous arms and cKO region will be generated by PCR using BAC clone RP23-147I23 as template. Cas9, gRNA and targeting vector will be co-injected into fertilized eggs for cKO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Exon 4 starts from about 43.77% of the coding region. The knockout of Exon 4 will result in frameshift of the gene. The size of intron 3 for 5'-loxP site insertion: 2468 bp, and the size of intron 4 for 3'-loxP site insertion: 859 bp. The size of effective cKO region: ~627 bp. The cKO region does not have any other known gene. Page 1 of 7 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele gRNA region 5' gRNA region 3' 1 4 5 Targeting vector Targeted allele Constitutive KO allele (After Cre recombination) Legends Exon of mouse Rbm7 Homology arm cKO region loxP site Page 2 of 7 https://www.alphaknockout.com Overview of the Dot Plot Window size: 10 bp Forward Reverse Complement Sequence 12 Note: The sequence of homologous arms and cKO region is aligned with itself to determine if there are tandem repeats.