40 Years of mRNA Splicing: from Discovery to Therapeutics

  • History and overview of mRNA splicing
  • Biology of Spliceosome
  • Introns, Exons and alternative splicing
  • Spliceosome complexes
  • Diseases of mRNA splicing
  • Therapeutic approaches to mRNA Splicing diseases

The discovery of mRNA splicing in 1977 established a new step in the central dogma of molecular biology, the “flow” of genetic information from DNA to RNA to the protein product. Our meeting will focus on forty years of advances in this field with topics such as the spliceosome, alternative RNA splicing, diseases related to RNA splicing, and therapeutics focused on RNA splicing. The meeting will encompass discussions not only of what has already been accomplished, but also how this history continues to shape the future.

Meeting is organized by Mila Pollock, Cold Spring Harbor Laboratory, Phil Sharp, Massachusetts Institute of Technology, & Joan Steitz, Yale University / HHMI.

What mRNA Splicing?

Spliceosome Diagram

mRNA splicing is essentially the editing of the precursor mRNA transcript copied from nuclear DNA into a mature mRNA molecule that can then be translated into a protein. Key to this process is the spliceosome, an RNA–protein complex that catalyzes the splicing reactions. Since its initial discovery in 1977, mRNA splicing has been revealed to be exquisitely complex as new technologies have evolved to study it in closer and closer detail.

The mRNA splicing process plays a large role in a wide range of diseases, including motor neuron diseases, muscle degenerative diseases, retinopathies, and cancers, to name a few. Disruptions in the splicing process via mutation have been estimated to comprise as much as 50% of human disease mutations. Deciphering the mechanisms of these mutations is essential to developing effective therapies that can correct or inhibit the resulting pathological splicing events. Remedies being explored include antisense oligonucleotides, RNA-binding molecules, and chemicals that interact with splice site selection.


Previous History of Science Meetings

This meeting is the seventh in a series organized by the CSHL Meeting and Courses Department together with Genentech Center for the History of Molecular Biology and Biotechnology. We have invited speakers who made many of the seminal discoveries that began the field, as well as those who are working in the field now. Like the previous meetings in the series, this meeting will provide an excellent opportunity to look in depth at a topic and to share the stories that are often missing from academic accounts.

Previous meetings in the series include:

Organizers

  • Mila Pollock, Cold Spring Harbor Laboratory
  • Phil Sharp, Massachusetts Institute of Technology
  • Joan Steitz, Yale University/HHMI

Speakers

  • Manuel Ares, University of California, Santa Cruz
  • Gil Ast, Tel Aviv University
  • Jean D. Beggs, University of Edinburgh
  • Douglas L. Black, University of California, Los Angeles
  • Ben Blencowe, University of Toronto
  • Christopher B. Burge, Massachusetts Institute of Technology
  • Thomas Cech, University of Colorado, Boulder/HHMI
  • Benoit Chabot, University of Sherbrooke, Canada
  • Soo-Chen Cheng, Academia Sinica, Taipel, Taiwan
  • Louise T. Chow, University of Alabama at Birmingham
  • Nathaniel Comfort, John Hopkins University
  • Robert Darnell, The Rockefeller University
  • Gideon Dreyfuss, University of Pennsylvania School of Medicine/HHMI
  • Xiang-Dong Fu, University of California, San Diego
  • Mariano A. Garcia-Blanco, University of Texas Medical Branch/Duke-NUS Medical School, Singapore
  • Richard Gelinas, Institute for Systems Biology
  • Walter Gilbert, Harvard University
  • Brenton R. Graveley, UConn Health, Farmington, CT
  • Michael R. Green, National Institute of Allergy and Infectious Diseases
  • Nouria Hernandez, University of Lausanne, Switzerland
  • Ryszard Kole, Sarepta Therapeutics
  • Magda Konarska, The Rockefeller University
  • Alberto R. Kornblihtt, Universidad de Buenos Aires
  • Adrian R. Krainer, Cold Spring Harbor Laboratory
  • Angela Kramer, University of Geneva, Switzerland
  • Kristen W. Lynch, Perelman School of Medicine, University of Pennsylvania
  • Reinhard Lührmann, Max-Planck Institute for Biophysical Chemistry
  • Tom Maniatis, Columbia University College of Physicians and Surgeons
  • James L. Manley, Columbia University
  • Iain Mattaj, EMBL, Heidelberg Germany
  • Melissa J. Moore, University of Massachusetts Medical School
  • Stephen Mount, University of Maryland
  • Siddhartha Mukherjee, Columbia University Medical Center
  • Kiyoshi Nagai, MRC Laboratory of Molecular Biology, Cambridge
  • Karla M. Neugebauer, Yale University
  • Timothy Nilsen, Case Western Reserve University
  • Stu Orkin, Dana-Farber Cancer Institute
  • Rick Padgett, Cleveland Clinic
  • Phillip A. Sharp, Massachusetts Institute of Technology
  • Mila Pollock, Cold Spring Harbor Laboratory
  • Charles Query, Albert Einstein College of Medicine
  • Nikolaus Rajewsky, Max Delbruck Center for Molecular Medicine
  • Richard J. Roberts, Cold Spring Harbor Laboratory
  • Michael Rosbash, Brandeis University
  • Phillip A. Sharp, Massachusetts Institute of Technology
  • Yigong Shi, Tsinghua University, Beijing
  • Erik Sontheimer, University of Massachusetts Medical School
  • David L. Spector, Cold Spring Harbor Laboratory
  • Jonathan Staley, University of Chicago
  • Joan A. Steitz, Yale University/HHMI
  • Bruce Stillman, Cold Spring Harbor Laboratory
  • Woan-Yuh Tarn, Academia Sinica, Taipei, Taiwan
  • Juan Valcarcel, Center for Genomic Regulation, Barcelona
  • Larry Zipursky, UCLA/HHMI