Transcriptional Interferences in Cis Natural Antisense Transcripts of Humans and Mice
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Long Non‑Coding Rnas XIST and MALAT1 Hijack the PD‑L1 Regulatory Signaling Pathway in Breast Cancer Subtypes
ONCOLOGY LETTERS 22: 593, 2021 Long non‑coding RNAs XIST and MALAT1 hijack the PD‑L1 regulatory signaling pathway in breast cancer subtypes AMANY SAMIR1, REDA ABDEL TAWAB2 and HEND M. EL TAYEBI1 1Molecular Pharmacology Research Group, Department of Pharmacology and Toxicology, German University in Cairo, Cairo 11835; 2Department of General Surgery, Ain Shams University, Cairo 11772, Egypt Received July 18, 2020; Accepted January 14, 2021 DOI: 10.3892/ol.2021.12854 Abstract. Long non‑coding RNAs (lncRNAs) have attracted presence of lncRNAs. Therefore, the results of the present widespread attention as potential biological and patho‑ study indicated that although miR‑182‑5p exhibited an onco‑ logical regulators. lncRNAs are involved in several biological genic effect, XIST exerted a dominant effect on the regulation processes in cancer. Triple negative breast cancer (TNBC) is of the PD‑L1 signaling pathway via the inhibition of the onco‑ characterized by strong heterogeneity and aggressiveness. At genic function of MALAT1. present, the implication of microRNAs (miRs) and lncRNAs in immunotherapy has been poorly studied. Nevertheless, Introduction the blockade of immune checkpoints, particularly that of the programmed cell‑death protein‑1/programmed cell‑death In the context of tumor biology, the six hallmarks of cancer ligand‑1 (PD‑L1) axis, is considered as a principle approach in have been proposed to be associated with progressively breast cancer (BC) therapy. The present study aimed to inves‑ growing tumors and to be responsible for the complexity of tigate the interaction between immune‑modulatory upstream neoplastic diseases, and these are limitless replicative poten‑ signaling pathways of the PD‑L1 transcript that could enhance tial, evading apoptosis, self‑sufficiency in growth signals, personalized targeted therapy. -
Model-Based Integration of Genomics and Metabolomics Reveals SNP Functionality in Mycobacterium Tuberculosis
Model-based integration of genomics and metabolomics reveals SNP functionality in Mycobacterium tuberculosis Ove Øyåsa,b,1, Sonia Borrellc,d,1, Andrej Traunerc,d,1, Michael Zimmermanne, Julia Feldmannc,d, Thomas Liphardta,b, Sebastien Gagneuxc,d, Jörg Stellinga,b, Uwe Sauere, and Mattia Zampierie,2 aDepartment of Biosystems Science and Engineering, ETH Zurich, 4058 Basel, Switzerland; bSIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland; cDepartment of Medical Parasitoloy and Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; dUniversity of Basel, 4058 Basel, Switzerland; and eInstitute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland Edited by Ralph R. Isberg, Tufts University School of Medicine, Boston, MA, and approved March 2, 2020 (received for review September 12, 2019) Human tuberculosis is caused by members of the Mycobacterium infection of macrophages (29–32). Beyond analyses of individual tuberculosis complex (MTBC) that vary in virulence and transmis- laboratory strains, however, no systematic characterization and sibility. While genome-wide association studies have uncovered comparative analysis of intrinsic metabolic differences across several mutations conferring drug resistance, much less is known human-adapted MTBC clinical strains has been performed. about the factors underlying other bacterial phenotypes. Variation If the metabolic and other phenotypic diversity between in the outcome of tuberculosis infection and diseases has been MTBC strains contributes to and modulates pathogenicity, an attributed primarily to patient and environmental factors, but obvious question is: Which elements of the limited genetic di- recent evidence indicates an additional role for the genetic diver- versity in the MTBC are responsible for phenotypic strain di- sity among MTBC clinical strains. -
Biological Functions of Natural Antisense Transcripts Andreas Werner
Werner BMC Biology 2013, 11:31 http://www.biomedcentral.com/1741-7007/11/31 COMMENTARY Open Access Biological functions of natural antisense transcripts Andreas Werner Abstract The most common meaning of the term 'antisense tran- script' refers to a protein coding sense transcript and a In theory, the human genome is large enough to fully processed (capped, polyadenylated) antisense RNA keep its roughly 20,000 genes well separated. In with complementarity in exonic regions (Figure 1). The practice, genes are clustered; even more puzzling, in key issue of whether the antisense transcripts act as ex- many cases both DNA strands of a protein coding quisitely specific gene regulators or are simply transcrip- gene are transcribed. The resulting natural antisense tional waste that a cell has learned to live with is still a transcripts can be a blessing and curse, as many matter of controversy [2]. However, a study published in appreciate, or simply transcriptional trash, as others BMC Genomics reports conservation of natural antisense believe. Widespread evolutionary conservation, as transcripts at a large scale between human, rat and mouse, recently demonstrated, is a good indicator for which strongly suggests that there is biological sense to potential biological functions of natural antisense having antisense transcripts [3]. transcripts. See research article: http://www.biomedcentral.com/ Regulatory antisense transcripts 1471-2164/14/243 The most convincing way to demonstrate the biologi- cal significance of an antisense transcript is to interfere with its expression and demonstrate phenotypic conse- By the mid-1980s antisense transcription in mammalian quences or altered expression levels of the sense tran- genomes had already been described by a few isolated script. -
Thoughts About SLC16A2, TSIX and XIST Gene Like Sites in the Human Genome and a Potential Role in Cellular Chromosome Counting Martina Rinčić1, Ivan Y
Rinčić et al. Molecular Cytogenetics (2016) 9:56 DOI 10.1186/s13039-016-0271-7 HYPOTHESIS Open Access Thoughts about SLC16A2, TSIX and XIST gene like sites in the human genome and a potential role in cellular chromosome counting Martina Rinčić1, Ivan Y. Iourov2,3,4 and Thomas Liehr5* Abstract Background: Chromosome counting is a process in which cells determine somehow their intrinsic chromosome number(s). The best-studied cellular mechanism that involves chromosome counting is ‘chromosome-kissing’ and X-chromosome inactivation (XCI) mechanism. It is necessary for the well-known dosage compensation between the genders in mammals to balance the number of active X-chromosomes (Xa) with regard to diploid set of autosomes. At the onset of XCI, two X-chromosomes are coming in close proximity and pair physically by a specific segment denominated X-pairing region (Xpr) that involves the SLC16A2 gene. Results: An Ensembl BLAST search for human and mouse SLC16A2/Slc16a2 homologues revealed, that highly similar sequences can be found at almost each chromosome in the corresponding genomes. Additionally, a BLAST search for SLC16A2/TSIX/XIST (genes responsible for XCI) reveled that “SLC16A2/TSIX/XIST like sequences” cover equally all chromosomes, too. With respect to this we provide following hypotheses. Hypotheses: If a single genomic region containing the SLC16A2 gene on X-chromosome is responsible for maintaining “balanced” active copy numbers, it is possible that similar sequences or gene/s have the same function on other chromosomes (autosomes). SLC16A2 like sequences on autosomes could encompass evolutionary older, but functionally active key regions for chromosome counting in early embryogenesis. -
Small Rnas and the Regulation of Cis-Natural Antisense Transcripts in Arabidopsis
UC Riverside UC Riverside Previously Published Works Title Small RNAs and the regulation of cis-natural antisense transcripts in Arabidopsis Permalink https://escholarship.org/uc/item/66p3c9bz Journal BMC Molecular Biology, 9 ISSN 1471-2199 Authors Jin, Hailing Vacic, Vladimir Girke, Thomas et al. Publication Date 2008 Peer reviewed eScholarship.org Powered by the California Digital Library University of California BMC Molecular Biology BioMed Central Research article Open Access Small RNAs and the regulation of cis-natural antisense transcripts in Arabidopsis Hailing Jin*1, Vladimir Vacic2, Thomas Girke3, Stefano Lonardi4 and Jian- Kang Zhu*3 Address: 1Departments of Plant Pathology & Microbiology, Center for Plant Cell Biology and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA, 2Computer Science and Engineering, University of California, Riverside, CA 92521, USA, 3Botany and Plant Sciences, Center for Plant Cell Biology and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA and 4Computer Science and Engineering, Center for Plant Cell Biology and Institute for Integrative Genome Biology, University of California, Riverside, CA 92521, USA Email: Hailing Jin* - [email protected]; Vladimir Vacic - [email protected]; Thomas Girke - [email protected]; Stefano Lonardi - [email protected]; Jian-Kang Zhu* - [email protected] * Corresponding authors Published: 14 January 2008 Received: 30 May 2007 Accepted: 14 January 2008 BMC Molecular Biology 2008, 9:6 doi:10.1186/1471-2199-9-6 This article is available from: http://www.biomedcentral.com/1471-2199/9/6 © 2008 Jin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. -
6.047/6.878 Lecture 4: Comparative Genomics I: Genome Annotation Using Evolutionary Signatures
6.047/6.878 Lecture 4: Comparative Genomics I: Genome Annotation Using Evolutionary Signatures Mark Smith (Partially adapted from notes by: Angela Yen, Christopher Robde, Timo Somervuo and Saba Gul) 9/18/12 1 Contents 1 Introduction 4 1.1 Motivation and Challenge......................................4 1.2 Importance of many closely{related genomes...........................4 2 Conservation of genomic sequences5 2.1 Functional elements in Drosophila .................................5 2.2 Rates and patterns of selection...................................5 3 Excess Constraint 6 3.1 Causes of Excess Constraint.....................................7 3.2 Modeling Excess Constraint.....................................8 3.3 Excess Constraint in the Human Genome.............................9 3.4 Examples of Excess Constraint................................... 10 4 Diversity of evolutionary signatures: An Overview of Selection Patterns 10 4.1 Selective Pressures On Different Functional Elements....................... 11 5 Protein{Coding Signatures 12 5.1 Reading{Frame Conservation (RFC)................................ 13 5.2 Codon{Substitution Frequencies (CSFs).............................. 14 5.3 Classification of Drosophila Genome Sequences.......................... 16 5.4 Leaky Stop Codons.......................................... 17 6 microRNA (miRNA) genes 19 6.1 Computational Challenge...................................... 20 6.2 Unusual miRNA Genes........................................ 21 7 Regulatory Motifs 22 7.1 Computationally Detecting -
Antisense Transcription Licenses Nascent Transcripts to Mediate Transcriptional Gene Silencing
Downloaded from genesdev.cshlp.org on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Antisense transcription licenses nascent transcripts to mediate transcriptional gene silencing Yunkun Dang,1,4 Jiasen Cheng,2,4 Xianyun Sun,3 Zhipeng Zhou,1 and Yi Liu1 1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA; 2State Key Laboratory of Agricultural Microbiology, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China; 3State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, ZhongGuanCun, Beijing 100080, China In eukaryotes, antisense transcription can regulate sense transcription by induction of epigenetic modifications. We showed previously that antisense transcription triggers Dicer-independent siRNA (disiRNA) production and dis- iRNA locus DNA methylation (DLDM) in Neurospora crassa. Here we show that the conserved exonuclease ERI-1 (enhanced RNAi-1) is a critical component in this process. Antisense transcription and ERI-1 binding to target RNAs are necessary and sufficient to trigger DLDM. Convergent transcription causes stalling of RNA polymerase II during transcription, which permits ERI-1 to bind nascent RNAs in the nucleus and recruit a histone methyltransferase complex that catalyzes chromatin modifications. Furthermore, we show that, in the cytoplasm, ERI-1 targets hundreds of transcripts from loci without antisense transcription to regulate RNA stability. Together, our results demonstrate a critical role for transcription kinetics in long noncoding RNA-mediated epigenetic modifications and identify ERI-1 as an important regulator of cotranscriptional gene silencing and post-transcriptional RNA metabolism. [Keywords: DNA methylation; Neurospora; antisense transcription; gene silencing; small RNA] Supplemental material is available for this article. -
The Epigenetics of Non-Coding RNA
CHAPTER 4 The Epigenetics of Non-coding RNA Lesley J. Collins1, Barbara Schönfeld2,3, and Xiaowei Sylvia Chen4 1Massey Genome Service, Massey University, Palmerston North, New Zealand 2Allan Wilson Centre for Molecular Ecology and Evolution, Massey University, Palmerston North, New Zealand 3Institute of Molecular BioSciences, Massey University, Palmerston North, New Zealand 4Department of Biochemistry, University of Otago, Dunedin 9054, New Zealand INTRODUCTION Non-protein-coding RNAs (ncRNAs) are RNAs that are transcribed from DNA but are not translated into proteins. Many are functional and are involved in the processing and regulation of other RNAs such as mRNA, tRNA, and rRNA. Processing-type ncRNAs include small nuclear RNAs (snRNAs) involved in splicing, small nucleolar RNAs (snoRNAs) that 49 modify nucleotides in rRNAs and other RNAs, and RNase P that cleaves pre-tRNAs. Other small ncRNAs such as microRNAs (miRNAs) and short interfering RNAs (siRNAs) are involved in the regulation of target mRNAs and chromatin. Although many of these latter ncRNA classes are grouped under the term RNA interference (RNAi), it has become clear that there are many different ways that ncRNAs can interact with genes to up-regulate or down-regulate expression, to silence translation, or guide methylation [1–3]. Adding to these classes are long ncRNAs (typically 200 nt) that have also been implicated in gene regulation [4]. All of these ncRNAs form a network of processes, the RNA-infrastructure [2] that spans the cell not only spatially as RNAs move across the cell, but also temporally as the RNAs regulate gene processes during the cell cycle. Thus, the regulation of RNA processes may not only be transcriptional or translational, but also from their biogenesis and processing pathways [2]. -
The Distribution and Evolution of Arabidopsis Thaliana Cis Natural Antisense Transcripts Johnathan Bouchard, Carlos Oliver and Paul M Harrison*
Bouchard et al. BMC Genomics (2015)16:444 DOI 10.1186/s12864-015-1587-0 RESEARCH ARTICLE Open Access The distribution and evolution of Arabidopsis thaliana cis natural antisense transcripts Johnathan Bouchard, Carlos Oliver and Paul M Harrison* Abstract Background: Natural antisense transcripts (NATs) are regulatory RNAs that contain sequence complementary to other RNAs, these other RNAs usually being messenger RNAs. In eukaryotic genomes, cis-NATs overlap the gene they complement. Results: Here, our goal is to analyze the distribution and evolutionary conservation of cis-NATs for a variety of available data sets for Arabidopsis thaliana, to gain insights into cis-NAT functional mechanisms and their significance. Cis-NATs derived from traditional sequencing are largely validated by other data sets, although different cis-NAT data sets have different prevalent cis-NAT topologies with respect to overlapping protein-coding genes. A. thaliana cis-NATs have substantial conservation (28-35% in the three substantive data sets analyzed) of expression in A. lyrata. We examined evolutionary sequence conservation at cis-NAT loci in Arabidopsis thaliana across nine sequenced Brassicaceae species (picked for optimal discernment of purifying selection), focussing on the parts of their sequences not overlapping protein- coding transcripts (dubbed ‘NOLPs’). We found significant NOLP sequence conservation for 28-34% NATs across different cis-NAT sets. This NAT NOLP sequence conservation versus A. lyrata is generally significantly correlated with conservation of expression. We discover a significant enrichment of transcription factor binding sites (as evidenced by CHIP-seq data) in NOLPs compared to randomly sampled near-gene NOLP-like DNA , that is linked to significant sequence conservation. -
Strand-Specific RNA-Seq Reveals Widespread Occurrence of Novel Cis
Lu et al. BMC Genomics 2012, 13:721 http://www.biomedcentral.com/1471-2164/13/721 RESEARCH ARTICLE Open Access Strand-specific RNA-seq reveals widespread occurrence of novel cis-natural antisense transcripts in rice Tingting Lu1*, Chuanrang Zhu1, Guojun Lu1, Yunli Guo1, Yan Zhou1, Zhiyong Zhang2, Yan Zhao1, Wenjun Li1, Ying Lu1, Weihua Tang2, Qi Feng1 and Bin Han1* Abstract Background: Cis-natural antisense transcripts (cis-NATs) are RNAs transcribed from the antisense strand of a gene locus, and are complementary to the RNA transcribed from the sense strand. Common techniques including microarray approach and analysis of transcriptome databases are the major ways to globally identify cis-NATs in various eukaryotic organisms. Genome-wide in silico analysis has identified a large number of cis-NATs that may generate endogenous short interfering RNAs (nat-siRNAs), which participate in important biogenesis mechanisms for transcriptional and post-transcriptional regulation in rice. However, the transcriptomes are yet to be deeply sequenced to comprehensively investigate cis-NATs. Results: We applied high-throughput strand-specific complementary DNA sequencing technology (ssRNA-seq) to deeply sequence mRNA for assessing sense and antisense transcripts that were derived under salt, drought and cold stresses, and normal conditions, in the model plant rice (Oryza sativa). Combined with RAP-DB genome annotation (the Rice Annotation Project Database build-5 data set), 76,013 transcripts corresponding to 45,844 unique gene loci were assembled, in which 4873 gene loci were newly identified. Of 3819 putative rice cis-NATs, 2292 were detected as expressed and giving rise to small RNAs from their overlapping regions through integrated analysis of ssRNA-seq data and small RNA data. -
Application of Comparative Genomics for Detection of Genomic Features and Transcriptional Regulatory Elements Hong Lu Iowa State University
Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2011 Application of comparative genomics for detection of genomic features and transcriptional regulatory elements Hong Lu Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Cell and Developmental Biology Commons, and the Genetics and Genomics Commons Recommended Citation Lu, Hong, "Application of comparative genomics for detection of genomic features and transcriptional regulatory elements" (2011). Graduate Theses and Dissertations. 12151. https://lib.dr.iastate.edu/etd/12151 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Application of comparative genomics for detection of genomic features and transcriptional regulatory elements by Hong Lu A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Bioinformatics and Computational Biology Program of Study Committee: Volker Brendel, Co-major Professor Roger Wise, Co-major Professor Julie Dickerson Nick Lauter Adam Bogdanove Iowa State University Ames, Iowa 2011 Copyright © Hong Lu, 2011. All rights reserved. ii TABLE OF CONTENTS CHAPTER 1. INTRODUCTION -
XIST RNA and the Mechanism of X Chromosome Inactivation, Kathrin Plath, Susanna Mlynarczyk-Evans, Dmitri A
10 Sep 2002 21:18 AR AR174-GE36-10.tex AR174-GE36-10.SGM LaTeX2e(2002/01/18) P1: IBC 10.1146/annurev.genet.36.042902.092433 Annu. Rev. Genet. 2002. 36:233–78 doi: 10.1146/annurev.genet.36.042902.092433 Copyright c 2002 by Annual Reviews. All rights reserved XIST RNA AND THE MECHANISM OF XCHROMOSOME INACTIVATION Kathrin Plath, Susanna Mlynarczyk-Evans, Dmitri A. Nusinow, and Barbara Panning Department of Biochemistry & Biophysics, University of California San Francisco, San Francisco, California 94143; e-mail: [email protected], [email protected], [email protected], [email protected] Key Words dosage compensation, imprinting, Tsix RNA, facultative heterochromatin, differentiation ■ Abstract Dosage compensation in mammals is achieved by the transcriptional inactivation of one X chromosome in female cells. From the time X chromosome inac- tivation was initially described, it was clear that several mechanisms must be precisely integrated to achieve correct regulation of this complex process. X-inactivation ap- pears to be triggered upon differentiation, suggesting its regulation by developmental cues. Whereas any number of X chromosomes greater than one is silenced, only one X chromosome remains active. Silencing on the inactive X chromosome coincides with the acquisition of a multitude of chromatin modifications, resulting in the formation of extraordinarily stable facultative heterochromatin that is faithfully propagated through subsequent cell divisions. The integration of all these processes requires a region of the X chromosome known as the X-inactivation center, which contains the Xist gene and its cis-regulatory elements. Xist encodes an RNA molecule that plays critical roles in the choice of which X chromosome remains active, and in the initial spread and es- tablishment of silencing on the inactive X chromosome.