DOCSLIB.ORG

Nascent RNA and the Coordination of Splicing with Transcription

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Nascent RNA and the Coordination of Splicing with Transcription Downloaded from http://cshperspectives.cshlp.org/ on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press Nascent RNA and the Coordination of Splicing with Transcription Karla M. Neugebauer Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 Correspondence: [email protected] SUMMARY At each active protein-encoding gene, nascent RNA is tethered to the DNA axis by elongating RNA polymerase II (Pol II) and is continuously altered by splicing and other processing events during its synthesis. This review discusses the development of three major methods that ena- ble us to track the conversion of precursor messenger RNA (pre-mRNA) to messenger RNA (mRNA) products in vivo: live-cell imaging, metabolic labeling of RNA, and RNA-seq of purified nascent RNA. These approaches are complementary, addressing distinct issues of transcription rates and intron lifetimes alongside spatial information regarding the gene posi- tion of Pol II at which spliceosomes act. The findings will be placed in the context of active transcription units, each of which—because of the presence of nascent RNA, Pol II, and features of the chromatin environment—will recruit a potentially gene-specific constellation of RNA binding proteins and processing machineries. Outline 1 Introduction 5 The coordination of splicing with transcription 2 Quantification of splicing relative to transcription using chromatin-based assays 6 Concluding remarks 3 Quantification of splicing rates through References RNA metabolic labeling 4 Quantification of splicing rates through live-cell fluorescence imaging Editors: Thomas R. Cech, Joan A. Steitz, and John F. Atkins Additional Perspectives on RNA Worlds available at www.cshperspectives.org Copyright # 2019 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a032227 Cite this article as Cold Spring Harb Perspect Biol 2019;11:a032227 1 Downloaded from http://cshperspectives.cshlp.org/ on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press K.M. Neugebauer 1 INTRODUCTION ing approaches to provide key insights into the coordination of precursor messenger RNA (pre-mRNA) processing with Gene expression begins with the synthesis of RNA from the transcription. DNA template by RNA polymerase. The steady state level of What proportion of introns are removed concurrently any RNA in the cell reflects the balance between its syn- with transcription? Global studies have approached this thesis and degradation by specific enzymes; yet, many re- question by purifying nascent RNA from a chromatin actions take place between these two end points. One fraction and preparing RNA-seq libraries or probes for implicit goal of next-generation RNA sequencing (RNA- high-density tiling arrays. Co-transcriptional splicing fre- seq) is to characterize all possible RNAs expressed in cells ′ quencies were similarly high in budding yeast (75%), fly from their 5 ends—indicative of transcription start sites ′ ′ (83%), and human (74%–85%) cell lines and tissues, al- (TSSs)—to their 3 ends—indicative of 3 -end formation. though a lower proportion (45%) was detected by analysis RNA-seq also reveals massive variation throughout tran- of mouse liver nascent RNA (Carrillo Oesterreich et al. script bodies. In the case of eukaryotic messenger RNA 2010; Ameur et al. 2011; Khodor et al. 2011; Khodor et al. (mRNA), this variation is the result of splicing, editing, ′ 2012; Tilgner et al. 2012). Validation of RNA-seq and array nucleotide modification, and 3 -end cleavage and polyade- data by quantitative reverse transcription polymerase chain nylation, each of which is subject to regulation. A second reaction (RT-qPCR) strengthened and extended these find- goal of RNA-seq is to quantify RNA levels in cells. Standard ings (Carrillo Oesterreich et al. 2010; Ameur et al. 2011). analysis of mRNA reports on steady state levels of the prod- General agreement with these numbers came from meta- ucts of all of these reactions and can generate hypotheses bolic labeling (Windhager et al. 2012) and protein biochem- about what may have occurred during an mRNA’s lifetime. istry and immunofluorescence, showing that most active Because each step of mRNA processing at least begins spliceosomes are associated with chromatin (Girard et al. co-transcriptionally (Fig. 1), sequencing of nascent RNA 2012). That said, not all intron removal is co-transcription- provides evidence of the precursors, intermediates, and al. In particular, terminal introns are least well removed products. In the past decade, these next-generation se- co-transcriptionally, in agreement with RT-PCR studies quencing applications have complemented live-cell imag- of individual endogenous genes (Schmidt et al. 2011; Tilgner et al. 2012). Furthermore, 20% of activated spliceosomes in the cell are not chromatin-associated (Girard et al. 2012), and constitutive splicing appears to be more co-transcrip- tional than alternative splicing (Ameur et al. 2011; Khodor et al. 2011; Tilgner et al. 2012). Moreover, particular cell types use intron retention or detention as a regulatory step A (Pandya-Jones et al. 2013; Wong et al. 2013; Braunschweig A A et al. 2014; Boutz et al. 2015; Pimentel et al. 2016). Taken A together, global studies indicate that most introns are re- moved co-transcriptionally despite differences in species, ′ ′ 5 SS 3 SS cell types, and analysis methods (Brugiolo et al. 2013). Capping Splicing Co-transcriptional pre-mRNA processing events can be Polyadenylation coupled physically or temporally to one another, to chro- matin, and/or to RNA polymerase II (Pol II). Early evidence Figure 1. Co-transcriptional RNA processing of eukaryotic protein- coding genes. Schematic diagram depicting a eukaryotic gene with its that transcription-splicing coupling is an important deter- transcription start site (forward arrow), two annotated exons (thick minant of gene expression came from the analysis of mRNA boxes), and one intron (line). The 5′ end of the annotated intron, or products in response to changes in coupling. For example, 5′ splice site, and the 3′ end, the 3′ splice site, are marked 5′SS and ′ ′ the 5 -end capping enzymes physically associate with Pol II 3 SS, respectively. RNA polymerase II (Pol II) (oval) moves from left carboxy-terminal domain (CTD) heptad repeats that are to right with varying speeds indicated by the forward arrowheads, including pausing marked with a pause symbol. The nascent RNA phosphorylated on serine 5 and are allosterically stimulated (exons depicted with dashed lines and intron with solid line) emerges by this interaction (Cho et al. 1997; McCracken et al. 1997a; from Pol II as elongation proceeds. The nascent RNA 5′ end imme- Cho et al. 1998). When the CTD is truncated, capping fails diately receives a 7-methylguanosine cap (black ball), and cleavage at to occur and mRNA becomes degraded (McCracken et al. the polyadenylation site releases the nascent RNA from Pol II. Many 1997b). It is currently unclear how the exosome gains access splicing events occur after capping and before poly(A) cleavage. The 5′SS and 3′SS are depicted in the nascent RNA as open circles, and to unspliced RNA and whether some proportion of RNA spliceosome assembly is indicated by looping out of the intron. The escapes capping. An example of “kinetic” coupling between intron lariat and spliced nascent RNA products are shown. splicing and transcription is the observation that global 2 Cite this article as Cold Spring Harb Perspect Biol 2019;11:a032227 Downloaded from http://cshperspectives.cshlp.org/ on October 3, 2021 - Published by Cold Spring Harbor Laboratory Press The Coordination of Splicing with Transcription patterns of alternative splicing are dependent on Pol II nascent RNA, and electron-dense ribonucleoprotein (RNP) elongation rates, which are slowed or accelerated on ultra- particles attached to the nascent RNA were visualized in violet (UV) damage, chromatin modification, and direct these striking images. RNP particles 25 and 40 nm in diam- mutation of Pol II (Munoz et al. 2009; Luco et al. 2011; eter were separated by an RNA loop and appeared at pre- Hnilicova et al. 2013; Schor et al. 2013; Dujardin et al. dictable sites along nascent RNA, suggesting they are 2014; Fong et al. 2014). In considering how splicing and components of the assembling spliceosome. These studies transcription are coordinated with one another, an obvious measured DNA distance in µm to deduce that splicing oc- goal would be to determine in vivo transcription rates and, curred when Pol II had traveled 4.5 kb past the 3′SS (Fig. 2) independently, in vivo splicing rates. Quantifying the rate of (Beyer and Osheim 1988). Many of the observations made co-transcriptional splicing and the relative position of Pol II using chromosome spreading methods are consistent with when splicing occurs is discussed in the following sections. findings in the Balbiani ring of Chironomus tentans, where These splicing rates will inevitably be confounded by the it has been possible to dissect out chromosomal regions and transcription rates. infer co-transcriptional splicing by RT-PCR and other Pol II transcription elongation rates have been cal- methods (Bauren and Wieslander 1994; Bjork and Wies- culated from metabolic labeling data, timed chromatin lander 2015). Although the harsh conditions of chromatin immunoprecipitation (ChIP) experiments, or fluorescence spreading unfold nascent RNA for analysis, electron to- imaging and are available for specific genes or gene
Load more

Recommended publications
  • SRSF1 Splicing by Transcription Dynamics
    T Cell Activation Regulates CD6 Alternative Splicing by Transcription Dynamics and SRSF1 This information is current as Vânia G. da Glória, Mafalda Martins de Araújo, Ana of June 23, 2014. Mafalda Santos, Rafaela Leal, Sérgio F. de Almeida, Alexandre M. Carmo and Alexandra Moreira J Immunol 2014; 193:391-399; Prepublished online 2 June 2014; Downloaded from doi: 10.4049/jimmunol.1400038 http://www.jimmunol.org/content/193/1/391 Supplementary http://www.jimmunol.org/content/suppl/2014/05/31/jimmunol.140003 http://www.jimmunol.org/ Material 8.DCSupplemental.html References This article cites 67 articles, 30 of which you can access for free at: http://www.jimmunol.org/content/193/1/391.full#ref-list-1 Subscriptions Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscriptions by Alexandre Carmo on June 23, 2014 Permissions Submit copyright permission requests at: http://www.aai.org/ji/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/cgi/alerts/etoc The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 9650 Rockville Pike, Bethesda, MD 20814-3994. Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology T Cell Activation Regulates CD6 Alternative Splicing by Transcription Dynamics and SRSF1 Vaˆnia G. da Glo´ria,* Mafalda Martins de Arau´jo,†,‡,x Ana Mafalda Santos,† Rafaela Leal,* Se´rgio F. de Almeida,{ Alexandre M. Carmo,†,‖ and Alexandra Moreira* The T cell-surface glycoprotein CD6 is a modulator of cellular responses and has been implicated in several autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and psoriasis.
    [Show full text]
  • People & Ideas
    People & Ideas Alberto Kornblihtt: Coupling alternative splicing with transcription Melina Casadio Kornblihtt studies how gene expression is controlled in mammals and plants. Alberto Kornblihtt was raised in Buenos its alternative exons promotes G9a nuclear Aires, Argentina. His parents both taught localization and neuron differentiation. (mathematics and geography), and his sib- Another aspect of our research re- lings pursued careers in science and teach- lates to chromatin and the nuclear effects ing, attesting to the passion for knowledge of the small RNA machinery. The prev- and education instilled by their parents. alent view is that, in mammalian cells, Kornblihtt always knew that he would be a argonaute proteins only function in the scientist, and he settled on biology in high cytoplasm through a mechanism known school after learning about DNA, RNA, pro- as posttranscriptional gene silencing. This teins, and the genetic code from the plant view neglects the existence of the nuclear taxonomist Rosa Guaglianone. High school mechanism known as transcriptional gene also marked his introduction to Joachim silencing in these cells. However, we Hämmerling’s 1943 experiments, which showed that siRNAs play nuclear roles show that the morphology of the single-cell in the control of alternative pre-mRNA Alberto Kornblihtt. PHOTO COURTESY OF THE BERLIN FEBS MEETING, 2015. alga Acetabularia is controlled by the nu- splicing (2). siRNAs targeting intronic se- cleus. His interest in the regulation of gene quences close to an alternative exon
    [Show full text]
  • RNA Control and Regulation
    This is a free sample of content from Cold Spring Harbor Symposium on Quantitative Biology. Volume LXXXIV: RNA Control and Regulation. Click here for more information on how to buy the book. Foreword The Cold Spring Harbor Symposia on Quantitative Biology series is now in its 84th year, having been initiated by then-Director Reginald Harris back in 1933 when the Symposium lasted a full month! The Cold Spring Harbor Symposia bring together scientists to present and evaluate new data and ideas in rapidly moving areas of biological research. Each year, a topic is chosen at a stage at which general and intensive scrutiny and review are warranted. Many previous Cold Spring Harbor Symposia have addressed different aspects of RNA biology, including Nucleic Acids and Nucleoproteins in 1947, Transcription of Genetic Material in 1970, Mechanisms of Transcription in 1998, The Ribosome in 2001, and Regulatory RNAs in 2006. The enormous progress in the field in the past 15 years led us to conclude that the time was past due for another Symposium squarely focused on RNA. In fact, this is only the second Symposium in its entire history to include RNA in the title of the meeting, which we think conveys how central this molecule is in so many areas of the biology of the cell and increasingly to how we think about treating disease. Topics addressed at the 2019 Symposium included RNA-based structures; RNA modifications; nuclear localization of RNA; quality control and editing; RNA and gene regulation; cotranscriptional splicing; intron–exon boundaries; alternative polyadenylation; transposon control; small noncoding RNAs; long noncoding RNAs; RNA and development; membraneless organelles; phase separation; RNA-based diseases; and novel RNA functions.
    [Show full text]
  • In Red Those Papers That Are Part of the Exam (I.E. One Question Will Be To
    Readings Cotranscriptional RNA processing • The C‐terminal domain of RNA polymerase II couples mRNA processing to transcription.McCracken S, Fong N, Yankulov K, Ballantyne S, Pan G, Greenblatt J, Patterson SD, Wickens M, Bentley DL.Nature. 1997 Jan 23;385(6614):357‐61. • An extensive network of coupling among gene expression machines.Maniatis T, Reed R.Nature. 2002 Apr 4;416(6880): 499‐506. Review. • Curr Opin Cell Biol. 2005 Jun;17(3):262‐8.Promoter usage and alternative splicing.Kornblihtt AR. In red those papers that are part of the exam (i.e. one question will be to comment a figure) Readings pre mRNA splicing • Mechanism of Alternative pre mRNA splicing Douglas Black Annu Rev Biochem 2003 • Another step forward for SELEXive splicing.Buratti E, Baralle FE.Trends Mol Med. 2005 Jan;11(1):5‐9. Review. • Listening to silence and understanding nonsense: exonic mutations that affect splicing.Cartegni L, Chew SL, Krainer AR. Nat Rev Genet. 2002 Apr;3 (4):285‐98 • Determinants of SR protein specificity.Tacke R, Manley JL.Curr Opin Cell Biol. 1999 Jun;11(3):358‐62. Review. • Nat Struct Mol Biol. 2009 Sep;16(9):902‐3.When chromatin meets splicing.Kornblihtt AR, Schor IE, Allo M, Blencowe BJ. In red those papers that are part of the exam (i.e. one question will be to comment a figure) Readings polyA and RNA editing • HITS‐CLIP yields genome‐wide insights into brain alternative RNA processing. Licatalosi DD, et al (The CLIP identify NOVA as regulator of Alterantive PolyAdenilation) • Mechanisms and consequences of alternative polyadenylation.Di Giammartino DC, Nishida K, Manley JL.Mol Cell.
    [Show full text]
  • 2019 ANNUAL SMA CONFERENCE JUNE 28TH - JULY 1ST, 2019 DISNEYLAND HOTEL in ANAHEIM, CALIFORNIA Dear Families
    2019 ANNUAL SMA CONFERENCE JUNE 28TH - JULY 1ST, 2019 DISNEYLAND HOTEL IN ANAHEIM, CALIFORNIA Dear Families, We are leading the way to a world without spinal muscular atrophy. We fund and direct comprehensive research that drives breakthroughs in treatment and care, and we provide families the support they need for today. The FDA approval of Spinraza in December 2016 and the approval of Zolgensma last month were major steps toward that goal. As a community, we’ve celebrated those long-awaited breakthroughs, all the while recognizing that there remains more to be done. SMA is now changing. Individual needs and even our whole community are changing. We are expanding our research, WELCOME LETTER WELCOME care and support programs, while our commitment and community values remain the same as they have always been. As therapies are approved, research and care are more important than ever. We need to understand and optimize the impact of these therapies, and develop combination approaches and additional therapeutic targets to treat all ages, stages, and types of SMA, especially for teens and adults. One of our most important initiatives in this area is the SMA Care Center Network. The network now has 14 centers, and we will continue to add care centers across the US, to improve care and results, and to increase access to new therapies. We are increasingly shifting our programs to provide customized and local support. Examples of this include the 36 local Summits of Strength that we will have conducted across the country by the end of this year, and over 900 new adult support packages that we have delivered.
    [Show full text]
  • The in Vivo Dynamics of TCERG1, a Factor That Couples Transcriptional Elongation with Splicing
    Downloaded from rnajournal.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press The in vivo dynamics of TCERG1, a factor that couples transcriptional elongation with splicing NOEMÍ SÁNCHEZ-HERNÁNDEZ,1,4 STÉPHANIE BOIREAU,2 UTE SCHMIDT,2 JUAN PABLO MUÑOZ-COBO,1 CRISTINA HERNÁNDEZ-MUNAIN,3 EDOUARD BERTRAND,2 and CARLOS SUÑÉ1 1Department of Molecular Biology, Instituto de Parasitología y Biomedicina “López Neyra” (IPBLN-CSIC), PTS, Granada 18016, Spain 2Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, 34293 Montpellier, France 3Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina “López Neyra” (IPBLN-CSIC), PTS, Granada 18016, Spain ABSTRACT Coupling between transcription and RNA processing is key for gene regulation. Using live-cell photobleaching techniques, we investigated the factor TCERG1, which coordinates transcriptional elongation with splicing. We demonstrate that TCERG1 is highly mobile in the nucleoplasm and that this mobility is slightly decreased when it is associated with speckles. Dichloro-1-β- D-ribofuranosylbenzimidazole (DRB) but not α-amanitin treatment reduced the mobility of TCERG1, which suggests interaction with paused transcription elongation complexes. We found that TCERG1 mobility is rapid at the transcription site (TS) of a reporter that splices post-transcriptionally and that TCERG1 is recruited to the active TS independent of the CTD of RNAPII, thus excluding phosphorylated CTD as a requirement for recruiting this factor to the TS. Importantly, the mobility of TCERG1 is reduced when the reporter splices cotranscriptionally, which suggests that TCERG1 forms new macromolecular complexes when splicing occurs cotranscriptionally. In this condition, spliceostatin A has no effect, indicating that TCERG1 rapidly binds and dissociates from stalled spliceosomal complexes and that the mobility properties of TCERG1 do not depend on events occurring after the initial spliceosome formation.
    [Show full text]
  • SAIB - 52Th Annual Meeting Argentine Society for Biochemistry and Molecular Biology
    52th Annual Meeting Argentine Society for Biochemistry and Molecular Biology LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular Pabellón Argentina. Universidad Nacional de Córdoba November 7-10, 2016 BIOCELL 40 (Suppl.1) 2016 - SAIB - 52th Annual Meeting Argentine Society for Biochemistry and Molecular Biology LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular November 7th–10th, 2016 Córdoba, República Argentina Pabellón Argentina Universidad Nacional de Cordoba Cover Page: Confocal microscopy images of Arabidopsis thaliana root are displayed in the cover. The selected roots are expressing a GFP reporter of a mitotic cyclin (CYCB1;1-GFP, green), also they are counterstained with propidium iodide (IP, red) to display the cell structure. In order to follow the progression through the cell cycle phases, the root cells were synchronized in S phase using HU, and after pictures were taken every 2 hours. This type of experiment was also used to generate RNA samples to analyze the dynamics of different gene expression during the cell cycle. Inside the circle, which shows the cell cycle phases, images of cells expressing a histone fused to the fluorescent protein VENUS and stained with IP, are displayed. Those images allow following the steps of mitosis in vivo inside the root ( PL-P56: Identification of cell cycle regulators inplants, by Goldy, C; Ercoli, MF; Vena, R; Palatnik, J, Rodriguez, Ramiro E.) Diseño de tapa: Natalia Monjes 1 BIOCELL 40 (Suppl.1) 2016 MEMBERS OF THE SAIB BOARD José Luis Bocco President CIBICI-CONICET Facultad de Ciencias Químicas Universidad Nacional de Córdoba Silvia Moreno Vicepresident IQUIBICEN-CONICET Facultad de Cs Exactas y Naturales Universidad de Buenos Aires Carlos Andreo Past President CEFOBI-CONICET Facultad de Cs Bioquímicas y Farm.
    [Show full text]
  • Transcription and Mrna Processing Get Even Closer
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Cell, Vol. 120, 163–166, January 28, 2005, Copyright ©2005 by Elsevier Inc. DOI 10.1016/j.cell.2005.01.002 The Spanish Connection: Meeting Review Transcription and mRNA Processing Get Even Closer Manuel Ares, Jr.1,* and Nick J. Proudfoot2,* place before elongation can fully proceed (Figure 1A). 1Department of Molecular Cell At early elongation, the C-terminal domain (CTD) of the and Developmental Biology Pol II large subunit (Rpb1) becomes phosphorylated on University of California, Santa Cruz serine 5 positions within its characteristic heptad re- Santa Cruz, California 95064 peats. Ser5 phosphorylation at CTD recruits the mRNA 2Sir William Dunn School of Pathology capping complex, which adds a cap to the initial nascent University of Oxford transcript. Ser5 phosphorylation is also associated with South Parks Road specific nucleosomal marks at the 5Ј end of the gene, Oxford OX1 3RE such as histone H3 lysine 4 trimethylation (Hampsey United Kingdom and Reinberg, 2003). Several presentations dwelt on new aspects of cou- pling during early transcription elongation. John Lis (Cornell University, New York) described the presence The synthesis of mRNA by RNA polymerase II appears of the elongation factor TFIIS on RNA polymerase II that coupled to numerous RNA-processing events, based is paused at the beginning of Drosophila heat shock on physical or functional connections revealed by bio- genes prior to heat induction. During normal elongation, chemical or genetic tests. New findings were pre- TFIIS is thought to promote cleavage of those tran- sented at a recent meeting in Spain that begin to illumi- scripts whose 3Ј ends are misaligned in the polymerase nate the mechanisms underlying the connections active site, thus allowing polymerase to escape tran- between mRNA processing and specific steps in tran- script arrest (Fish and Kane, 2002).
    [Show full text]
  • Cure SMA Awards 10 New Grants in Basic Research
    BASIC RESEARCH DRUG DISCOVERY CLINICAL TRIALS CLINICAL CARE RESEARCHER MEETING LATEST ADVANCES COMPASS A Publication Dedicated to Research Updates | SUMMER 2017 Cure SMA Awards 10 New Grants in Basic Research In this issue of Compass, we are proud to Our hope is that Spinraza is just the leading edge of a robust drug pipeline, with a breadth and depth that reflects our goal announce over $1.03 million in new funding. of treatments for all ages, stages, and types of SMA. We’ve seen many advances in recent years, from new techniques Basic Research Grants in gene therapy, which Cure SMA is funding with an award Basic research is the first step in our comprehensive research to Nationwide Children’s Hospital through our transla- model. We fund basic research to investigate the biology and tional grant program, to drugs that affect muscle and nerve cause of SMA, in order to identify the most effective strategies function that could be used in combination with drugs like for drug discovery. We also use this funding to develop tools Spinraza that target the underlying genetics of SMA. We’re that facilitate SMA research. actively working on additional treatments that target the underlying genetics of SMA as well as therapies that target Without basic research, the SMA drug pipeline would not other systems, pathways, and processes affected by SMA. Our continue to grow and diversify. We need both a breadth and goal is a combination of therapeutic approaches that can be a depth of options in our quest for a maximally effective SMA tailored to each individual SMA patient.
    [Show full text]
  • Communicative & Integrative Biology Playing Inside the Genes
    This article was downloaded by: [Universidad de Buenos Aires] On: 18 August 2015, At: 10:06 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: 5 Howick Place, London, SW1P 1WG Communicative & Integrative Biology Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/kcib20 Playing inside the genes Ignacio E. Schora & Alberto R. Kornblihtta a Laboratorio de Fisiología y Biología Molecular, Departamento de Fisiología, Biología Molecular y Celular, IFIBYNE‑CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires Published online: 31 Aug 2009. To cite this article: Ignacio E. Schor & Alberto R. Kornblihtt (2009) Playing inside the genes, Communicative & Integrative Biology, 2:4, 341-343, DOI: 10.4161/cib.2.4.8550 To link to this article: http://dx.doi.org/10.4161/cib.2.4.8550 PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Versions of published Taylor & Francis and Routledge Open articles and Taylor & Francis and Routledge Open Select articles posted to institutional or subject repositories or any other third-party website are without warranty from Taylor & Francis of any kind, either expressed or implied, including, but not limited to, warranties of merchantability, fitness for a particular purpose, or non-infringement. Any opinions and views expressed in this article are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis.
    [Show full text]
  • Making and Breaking the Message
    University of Massachusetts Medical School eScholarship@UMMS Open Access Articles Open Access Publications by UMMS Authors 2003-11-13 Making and breaking the message David A. Mangus University of Massachusetts Medical School Et al. Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/oapubs Part of the Microbiology Commons, and the Molecular Genetics Commons Repository Citation Mangus DA, van Hoof A. (2003). Making and breaking the message. Open Access Articles. https://doi.org/10.1186/gb-2003-4-11-346. Retrieved from https://escholarship.umassmed.edu/oapubs/ 608 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Open Access Articles by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. Meeting report Making and breaking the message comment David A Mangus* and Ambro van Hoof† Addresses: *Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. †Department of Microbiology and Molecular Genetics, University of Texas Health Sciences Center, 6431 Fannin JFB 1.700, Houston, TX 77030, USA. Correspondence: David A Mangus. E-mail: [email protected] reviews Published: 21 October 2003 Genome Biology 2003, 4:346 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2003/4/11/346 © 2003 BioMed Central Ltd reports Thomas Walz (Harvard Medical School, Boston, USA) all A report on the Cold Spring Harbor Laboratory meeting indicate that the active spliceosome (C complex) has three ‘Eukaryotic mRNA Processing’, Cold Spring Harbor, USA, 20- domains of density surrounding a central cavity.
    [Show full text]
  • Global Impact of RNA Polymerase II Elongation Inhibition on Alternative Splicing Regulation
    Downloaded from genome.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation Joanna Y. Ip1, 2, Dominic Schmidt3, 4, Qun Pan1, Arun K. Ramani1, Andrew G. Fraser1, 2, Duncan T. Odom3, 4 and Benjamin J. Blencowe1, 2, 5 1Banting and Best Department of Medical Research, Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario, Canada M5S 3E1 2Department of Molecular Genetics, University of Toronto, 1 King's College Circle Toronto, Ontario, Canada M5S 1A8 3Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 ORE United Kingdom. 4Department of Oncology, Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 OXZ United Kingdom. 5 Correspondence to: B.J. Blencowe Donnelly Centre, Room 1016 University of Toronto 160 College Street, Ontario, Canada M5S 3E1 Tel. 416-978-3016 Fax. 416-946-5545 [email protected] Key words: RNA polymerase II elongation, alternative splicing, Nonsense-mediated mRNA decay, microarray profiling, chromatin-immunoprecipitation, high-throughput sequencing, RNA binding protein 1 Downloaded from genome.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press ABSTRACT The rate of RNA polymerase II (pol II) elongation can influence splice site selection in nascent transcripts, yet the extent and physiological relevance of this kinetic coupling between transcription and alternative splicing (AS) is not well understood. We performed experiments to perturb pol II elongation and then globally compared AS patterns with genome-wide pol II occupancy. RNA binding and RNA processing functions were significantly enriched among the genes with pol II elongation inhibition- dependent changes in AS.
    [Show full text]