RNA Society Newsletter February 2012
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The Ribosome As a Regulator of Mrna Decay
www.nature.com/cr www.cell-research.com RESEARCH HIGHLIGHT Make or break: the ribosome as a regulator of mRNA decay Anthony J. Veltri1, Karole N. D’Orazio1 and Rachel Green 1 Cell Research (2020) 30:195–196; https://doi.org/10.1038/s41422-019-0271-3 Cells regulate α- and β-tubulin levels through a negative present. To address this, the authors mixed pre-formed feedback loop which degrades tubulin mRNA upon detection TTC5–tubulin RNCs containing crosslinker with lysates from of excess free tubulin protein. In a recent study in Science, Lin colchicine-treated or colchicine-untreated TTC5-knockout cells et al. discover a role for a novel factor, TTC5, in recognizing (either having or lacking abundant free tubulin, respectively). the N-terminal motif of tubulins as they emerge from the After irradiation, TTC5 only crosslinked to the RNC in lysates ribosome and in signaling co-translational mRNA decay. from cells that had previously been treated with colchicine; Cells use translation-coupled mRNA decay for both quality these data suggested to the authors that some other (unknown) control and general regulation of mRNA levels. A variety of known factor may prevent TTC5 from binding under conditions of low quality control pathways including Nonsense Mediated Decay free tubulin. (NMD), No-Go Decay (NGD), and Non-Stop Decay (NSD) specifi- What are likely possibilities for how such coupling between cally detect and degrade mRNAs encoding potentially toxic translation and mRNA decay might occur? One example to protein fragments or sequences which cause ribosomes to consider is that of mRNA surveillance where extensive studies in translate poorly or stall.1 More generally, canonical mRNA yeast have identified a large group of proteins that recognize degradation is broadly thought to be translation dependent, and resolve stalled RNCs found on problematic mRNAs and 1234567890();,: though the mechanisms that drive these events are not target those mRNAs for decay. -
Ribosomes Slide on Lysine-Encoding Homopolymeric a Stretches
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Crossref RESEARCH ARTICLE elifesciences.org Ribosomes slide on lysine-encoding homopolymeric A stretches Kristin S Koutmou1, Anthony P Schuller1, Julie L Brunelle1,2, Aditya Radhakrishnan1, Sergej Djuranovic3, Rachel Green1,2* 1Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, United States; 2Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, United States; 3Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, United States Abstract Protein output from synonymous codons is thought to be equivalent if appropriate tRNAs are sufficiently abundant. Here we show that mRNAs encoding iterated lysine codons, AAA or AAG, differentially impact protein synthesis: insertion of iterated AAA codons into an ORF diminishes protein expression more than insertion of synonymous AAG codons. Kinetic studies in E. coli reveal that differential protein production results from pausing on consecutive AAA-lysines followed by ribosome sliding on homopolymeric A sequence. Translation in a cell-free expression system demonstrates that diminished output from AAA-codon-containing reporters results from premature translation termination on out of frame stop codons following ribosome sliding. In eukaryotes, these premature termination events target the mRNAs for Nonsense-Mediated-Decay (NMD). The finding that ribosomes slide on homopolymeric A sequences explains bioinformatic analyses indicating that consecutive AAA codons are under-represented in gene-coding sequences. Ribosome ‘sliding’ represents an unexpected type of ribosome movement possible during translation. DOI: 10.7554/eLife.05534.001 *For correspondence: ragreen@ Introduction jhmi.edu Messenger RNA (mRNA) transcripts can contain errors that result in the production of incorrect protein products. -
Fall 2016 Is Available in the Laboratory of Dr
RNA Society Newsletter Aug 2016 From the Desk of the President, Sarah Woodson Greetings to all! I always enjoy attending the annual meetings of the RNA Society, but this year’s meeting in Kyoto was a standout in my opinion. This marked the second time that the RNA meeting has been held in Kyoto as a joint meeting with the RNA Society of Japan. (The first time was in 2011). Particular thanks go to the local organizers Mikiko Siomi and Tom Suzuki who took care of many logistical details, and to all of the organizers, Mikiko, Tom, Utz Fischer, Wendy Gilbert, David Lilley and Erik Sontheimer, for putting together a truly exciting and stimulating scientific program. Of course, the real excitement in the annual RNA meetings comes from all of you who give the talks and present the posters. I always enjoy meeting old friends and colleagues, but the many new participants in this year’s meeting particularly encouraged me. (Continued on p2) In this issue : Desk of the President, Sarah Woodson 1 Highlights of RNA 2016 : Kyoto Japan 4 Annual Society Award Winners 4 Jr Scientist activities 9 Mentor Mentee Lunch 10 New initiatives 12 Desk of our CEO, James McSwiggen 15 New Volunteer Opportunities 16 Chair, Meetings Committee, Benoit Chabot 17 Desk of the Membership Chair, Kristian Baker 18 Thank you Volunteers! 20 Meeting Reports: RNA Sponsored Meetings 22 Upcoming Meetings of Interest 27 Employment 31 1 Although the graceful city of Kyoto and its cultural months. First, in May 2016, the RNA journal treasures beckoned from just beyond the convention instituted a uniform price for manuscript publication hall, the meeting itself held more than enough (see p 12) that simplifies the calculation of author excitement to keep ones attention! Both the quality fees and facilitates the use of color figures to and the “polish” of the scientific presentations were convey scientific information. -
Curriculum Vitae, Nils G. Walter, Dr. Ing. (Chemistry)
Curriculum Vitae, Nils G. Walter, Dr. Ing. (Chemistry) Department of Chemistry, Rm. 2405 Phone: (734) 615-2060 930 N. University Ave. FAX: (734) 647-4865 University of Michigan E-mail: [email protected] Ann Arbor, MI 48109-1055 http://singlemolecule.lsa.umich.edu http://sites.lsa.umich.edu/walter-lab https://rna.umich.edu PROFESSIONAL EXPERIENCE FACULTY 2020-present Faculty Director of the Microscopy Core in the Biomedical Research Core Facilities (BRCF) 2018 Sabbatical Visitor, Chan Zuckerberg Biohub, San Francisco 2017-present Francis S. Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry, College of Literature, Science and the Arts 2016-present Founding Co-Director, Center for RNA Biomedicine, U. of Michigan; awarded a 5-year $10.2M Biosciences Initiative Award in 2018 to further build this grassroots, 150-faculty member effort 2016-present Professor of Biological Chemistry 2015-present Co-Director, Microfluidics in Biomedical Sciences Training Program 2015-present Associate Director, Michigan Post-baccalaureate Research Education Program (PREP) 2010-present Founding Director, Single Molecule Analysis in Real-Time (SMART) Center 2009-present Professor of Chemistry 2005-2009 Associate Professor of Chemistry 2006 Sabbatical Visitor, Harvard University, with Sunney Xie in Chemistry & Chemical Biology 2006 Distinguished Visitor, JILA, Boulder, with David Nesbitt 2002-2005 Dow Corning Assistant Professor of Chemistry 1999-2005 Assistant Professor of Chemistry 1999-present Member of the Biophysics (since 1999), Applied Physics (since 2000), Cellular & Molecular Biology (since 2001), and Chemical Biology (since 2005) Interdepartmental Graduate Programs University of Michigan, Ann Arbor POSTDOCTORATE 1996-1999 Postdoctoral Research Fellow with Prof. John M. Burke, University of Vermont; Subject: Biophysical Studies of the Hairpin Ribozyme 1995 Postdoctoral Research Fellow with Nobel laureate Prof. -
Interview with Melvin I. Simon
MELVIN I. SIMON (b. 1937) INTERVIEWED BY SHIRLEY K. COHEN May 24 and June 5, 2005 Melvin I. Simon ARCHIVES CALIFORNIA INSTITUTE OF TECHNOLOGY Pasadena, California Subject area Biology Abstract Interview in two sessions, May 24 and June 5, 2005, with Melvin I. Simon, Anne P. and Benjamin F. Biaggini Professor of Biological Sciences, emeritus, in the Division of Biology. Dr. Simon received his BS from City College of New York in 1959 and his PhD in biochemistry from Brandeis in 1963. After receiving his degree, he was a postdoctoral fellow with Arthur Pardee at Princeton for a year and a half and then joined the faculty of the University of California at San Diego. In 1978, Dr. Simon and his UCSD colleague John Abelson established the Agouron Institute in San Diego, focusing on problems in molecular biology. He (along with Abelson) joined the faculty of Caltech as a full professor in 1982, and he served as chair of the Biology Division from 1995 to 2000. http://resolver.caltech.edu/CaltechOH:OH_Simon_M In this interview, he discusses his education in Manhattan’s Yeshiva High School (where science courses were taught by teachers from the Bronx High School of Science), at CCNY, and as a Brandeis graduate student working working with Helen Van Vunakis on bacteriophage. Recalls his unsatisfactory postdoc experience at Princeton and his delight at arriving at UC San Diego, where molecular biology was just getting started. Discusses his work on bacterial organelles; recalls his and Abelson’s vain efforts to get UCSD to back a full-scale initiative in molecular biology and their subsequent founding of their own institute. -
Curriculum Vitae
1 CURRICULUM VITAE David Ross Engelke EDUCATION 1974 University of Wisconsin, Madison, B.S. (Biochemistry) 1979 Washington University, St. Louis, Ph.D. (Biological Chemistry) Advisor: Robert G. Roeder POSTDOCTORAL TRAINING 1979-1983 Postdoctoral Fellow, Department of Chemistry, University of California, San Diego, La Jolla, California, Advisor: John Abelson ACADEMIC APPOINTMENTS 1983-1989 Assistant Professor, Department of Biological Chemistry, The University of Michigan, Ann Arbor, Michigan 1989-1996 Associate Professor, Department of Biological Chemistry, The University of Michigan 1996-2015 Professor, Department of Biological Chemistry, University of Michigan 1995 Interim Director, Medical Scientist Training Program 1995-1998 Director, Cellular and Molecular Biology Ph.D. Program, The University of Michigan 1998-2007 Founding Director, Program in Biomedical Sciences, The University of Michigan 2000-2007 Assistant Dean, Graduate and Postdoctoral Studies, UM Medical School 2008-2012 Associate Dean, H. H. Rackham School of Graduate Studies University of Michigan 2009-2010 Founding Director, Michigan Postbaccalaureate Research Education Program (PREP) 2010-2015 Associate Director, Michigan PREP 2013-2015 Chair, Department of Biological Chemistry, University of Michigan 2015-present Professor of Chemistry, University of Colorado Denver | Anschutz Professor of Biochemistry and Molecular Genetics, UC Denver | Anschutz Dean of the Graduate School, UC Denver | Anschutz CONSULTING POSITIONS 1989-1994 Parke-Davis 1990/91 Merck Inc. 1994 NeXstar, -
CURRENT TECHNOLOGY and RESOURCE NEEDS the Specific and Primary Agouronpurposes Are to Perform Research in the Sciences
The Agouron Institute GEOBIOLOGY CURRENT TECHNOLOGY and RESOURCE NEEDS The specific and primary AGOURONpurposes are to perform research in the sciences INSTITUTEand in mathematics, to disseminate the results obtained therefrom, all to benefit mankind. Cover photo: Phototrophic sulfur and non-sulfur bacteria in an enrichment from a microbial mat reveal part of the enormous diversity of microorganisms. © 2001 The Agouron Institute 45 GEOBIOLOGY CURRENT TECHNOLOGY and RESOURCE NEEDS The Agouron Institute INTRODUCTION 3 GEOBIOLOGY: 5 Current Research General Overview 5 Advances in Probing The Rock Record 6 Advances in Molecular Biology and Genomics 9 Current Research Directions 11 Questions of What and When: Detecting Life in the Geologic Record 12 Molecular Fossils 12 Morphological Fossils 14 Isotopic Signatures 16 Question of Who and How: Deciphering the Mechanisms of Evolution 18 Genetic Diversity 18 Microbial Physiology 20 Eukaryotic Systems 23 Experimental Paleogenetics 25 GEOBIOLOGY: Resource Needs 29 An Intensive Training Course in Geobiology 30 A Postdoctoral Fellowship Program in Geobiology 31 Support for Specific Research Projects 32 REFERENCES 34 2 Agouron Institute had expanded considerably and had obtained additional funding from the NSF and the NIH. A group of molecular biologists and chemists were collaborating to exploit new technology in which synthetic oligonucleotides were used to direct specific mutations in genes. A crystallography group had been INTRODUCTION formed and they were collaborating with the molecular biologists to study the properties of the altered proteins. These were among the very first applications of the new technology to form what is now the very ith the discovery of recombi- large field of protein engineering. -
Biological Chemistry 2011 Newsletter a Letter from the Chair : Dr
0.2 -1 k obs (s ) 0.1 EFlred - 0 0 ESQ O2 EFlox + H2O 2 0.4 00 0.6 0 0.2 1 O 2 [O 2] (mM)mM .22 EFlred 0 ESQ O - EFl + H O 2 ox 2 2 10 O 2 .18 0 EFlred - ESQ O EFl + H2O 2 2 ox 0 4 1 O 5 .1 2 4 0 EFlred - 1 ESQ O2 EFlox + H2O 2 1 0. 0. O2 BiologicalNewsletter Chemistry 2011 A Letter from the Chair : Dr. William L. Smith Greetings from Ann Arbor to Friends, Colleagues, and Graduates laboratory are famously I’ll begin like I do most successful in developing years with an update on algorithms for protein the state of the Depart- structure predictions. He and his group were ment. As a reminder, Biological Chemistry is ranked No. 1 in both pro- one of six basic science departments in a medical tein structure and function prediction among more school with now 26 different departments and two than 200 groups in the most recent international new ones (Cardiovascular Surgery and Bioinformat- competition (http://zhanglab.ccmb.med.umich.edu/). ics) due to be instituted soon. We currently have 47 Dr. Daniel Southworth has recently been appointed faculty with appointments in Biological Chemistry to a tenure track appointment as an Assistant Profes- all of whom have shared responsibilities for teaching sor in Biological Chemistry with a research track ap- graduate, medical and undergraduate students. The pointment in the Life Sciences Institute. Most recent- Department averages about 35 graduate students in ly, Dan received his Ph.D. -
Conference Agenda - 9Th International Mrna Health Conference 2020 (Virtual) (All Times Shown As Eastern Standard Time, EST)
Conference Agenda - 9th International mRNA Health Conference 2020 (virtual) (All times shown as Eastern Standard Time, EST) Day 1: Monday, November 9 08:00-08:15 Welcome and Logistics Stephane Bancel and Melissa Moore 08:15-09:45 Session I: mRNA Biology and Translation Chair: Melissa Moore 08:15-08:40 Single-cell transcriptome imaging and cell atlas of complex tissues Xiaowei Zhuang (HHMI/Harvard Chemistry) Colliding ribosomes function as a gauge for activation of cellular stress Rachel Green (HHMI/Johns Hopkins Medical 08:40-09:05 responses School) 09:05-09:30 Development of RNA structures for cancer immunotherapy Kyuri Lee (Ewha Womans University) 09:30-09:45 Decoding mRNA translatability and stability from the 5’UTR Shu-Bing Qian (Cornell University) 09:45-09:55 Break 09:55-10:00 Keynote Introduction Stephane Bancel 10:00-10:45 Keynote Speaker Anthony Fauci (NIAID/NIH) 10:45-11:00 Break 11:00-12:55 Session II: Delivery Chair: Dan Siegwart 11:00-11:20 mRNA Delivery Dan Anderson (MIT) 11:20-11:40 Biomaterials strategies to enhance and prolong the effects of therapeutic mRNA William L. Murphy (U.Wisconsin-Madison) 11:40-12:00 Supramolecular assemblies for enhanced mRNA delivery Horacio Cabral (U. Tokyo) 12:00-12:20 Boosting intracellular delivery of messenger RNA Gaurav Sahay (OHSU) Advancing pulmonary delivery of mRNA therapeutics for the treatment of 12:20-12:40 John Androsavich (Translate Bio) genetic diseases COATSOME SS-Lipids as novel, biodegradable, ionizable Lipids for mRNA 12:40-12:55 Syed Reza (NOF America) Therapeutics and Vaccines -
California Meetings
California Meetings An artist’s rendering of what the Archean earth looked like at the time of the rise of oxygen. The Birth of Oxygen John Abelson This presentation was given at a meeting of the American Academy, held at the University of California, San Diego, on November 17, 2006. John Abelson is George Beadle Professor of Biology, Emeritus, at the California Institute of Technology, Adjunct Professor of Biochemistry at the University of California, San Francisco, and the President of the Agouron Institute. He has been a Fellow of the American Academy since 1985. We take it for granted that our atmosphere thesis was, after the origin of life itself, the The closely linked evolution of photosyn- contains oxygen, but we and most other ani- most important development in the history thesis and the evolution of the atmosphere is mals would die within minutes if the oxygen of our planet. About twelve times as much perhaps the best example of the interdepen- was removed. It is not widely appreciated energy is derived from the aerobic metabo- dence of biological and geological processes. that for half of the earth’s history there was lism of a molecule of glucose as the energy In chronicling the rise of oxygen, I will ½rst virtually no oxygen in the atmosphere. Oxy- obtained from anaerobic metabolism. With- describe photosynthesis and its origins. Then gen appeared 2.45 billion years ago, and it has out the invention of oxygenic photosynthe- I will turn to a discussion of the state of the been present ever since–though not always sis, multicellular organisms could not have earth and its atmosphere before and during at its present level of 21 percent. -
Mechanistic Studies of Non-Canonical Amino Acid Mutagenesis
bioRxiv preprint doi: https://doi.org/10.1101/2021.05.24.445427; this version posted June 3, 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-NC-ND 4.0 International license. Mechanistic studies of non-canonical amino acid mutagenesis Rachel C. Fleisher1,2,*, Nina Michael1,*, and Ruben L. Gonzalez, Jr.1,† 1Department of Chemistry, Columbia University, 3000 Broadway, MC3126, New York, NY 10027, USA 2Current Address: Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel *These authors contributed equally to this work †To whom correspondence should be addressed: Ruben L. Gonzalez Jr., Department of Chemistry, Columbia University, 3000 Broadway, MC3126, New York, NY 10027, USA, Tel.: (212) 854-1096; Fax: (212) 932-1289; Email: [email protected] When citing this paper, please use the following: Fleischer, R.C., Michael, N., and Gonzalez Jr. RL. 2021. Mechanistic studies of non-canonical amino acid mutagenesis. Methods in Enzymology. Vol. 656: Submitted. Abstract Over the past decade, harnessing the cellular protein synthesis machinery to incorporate non- canonical amino acids (ncAAs) into tailor-made peptides has significantly advanced many aspects of molecular science. More recently, groundbreaking progress in our ability to engineer this machinery for improved ncAA incorporation has led to significant enhancements of this powerful tool for biology and chemistry. By revealing the molecular basis for the poor or improved 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.05.24.445427; this version posted June 3, 2021. -
First-Principles Model of Optimal Translation Factors Stoichiometry
bioRxiv preprint doi: https://doi.org/10.1101/2021.04.02.438287; this version posted April 4, 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. First-principles model of optimal translation factors stoichiometry Jean-Benoît Lalanne1;2;# and Gene-Wei Li1;y 1Department of Biology, and 2Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. #Present address: Department of Genome Sciences, University of Washington, Seattle, WA 98105, USA. yCorresponding author: [email protected] Abstract Enzymatic pathways have evolved uniquely preferred protein expression stoichiometry in living cells, but our ability to predict the optimal abundances from basic properties remains underdeveloped. Here we report a biophysical, first-principles model of growth optimization for core mRNA transla- tion, a multi-enzyme system that involves proteins with a broadly conserved stoichiometry spanning two orders of magnitude. We show that a parsimonious flux model constrained by proteome allocation is sufficient to predict the conserved ratios of translation factors through maximization of ribosome usage The analytical solutions, without free parameters, provide an interpretable framework for the observed hierarchy of expression levels based on simple biophysical properties, such as diffusion con- stants and protein sizes. Our results provide an intuitive and quantitative understanding for the construction of a central process of life, as well as a path toward rational design of pathway-specific enzyme expression stoichiometry. 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.04.02.438287; this version posted April 4, 2021.