RNA interference and splicing.
The catalytic core of the spliceosome is yet to be identified but is associated with the pairing of U2 and U6 snRNAs. It is assumed that both the snRNAs and other spliceosome components, such as proteins, are important for stabilizing the catalytic site. We are testing the catalytic potential of U2 and U6 snRNAs for a transesterification reaction similar to the exon joining step which occurs at the 3’ splice site. In this case, we, in collaboration with David Bartel, have used combitorial oligonucleotide synthesis to produce a pool of 3x1014 different RNAs with 40 nucleotides of random sequence - U6 snRNA (doped with 3% random substitutions) - U2 snRNA (doped with 3% random substitutions) - 40 nucleotides of random sequence - 5’ exon sequence. We will select from this RNA pool catalytic RNAs which splice to a second RNA containing a 3’ splice site sequence attached to a biotin ligand. By repetition, incubating for RNA catalysis a selecting by affinity chromatography a PCR amplification a regenerating a RNA pool and incubating for RNA catalysis, we hope to identify U2-U6 snRNA structures that have catalytic activity. We will determine the relationship between these catalytic structures and the reactions occurring in the spliceosome.
Shortened Curriculum Vitae:
EDUCATION
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1966: 1969: |
B.A., Chemistry & Mathematics, Union College, Barbourville, KY Ph.D., Chemistry, University of Illinois, Urbana |
POSITIONS
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2000-date 1999-date: 1991-1999: 1991-1999: 1985-1991: 1982-1985: 1979-1999: 1974-1979: 1972-1974: 1971-1972: 1969-1971: 1966-1669: |
Director, The McGovern Institute for Brain Research Institute Professor, MIT Salvador E. Luria Professor of Biology, MIT Head, Department of Biology, MIT Director, Center for Cancer Research, MIT Associate Director, Center for Cancer Research, MIT Professor, Center for Cancer Research and Department of Biology, MIT Associate Professor, Center for Cancer Research and Department of Biology, MIT Senior Research Investigator, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York Postdoctoral Fellow, Cold Spring Harbor Laboratory Postdoctoral Fellow, California Institute of Technology Research Assistant, Department of Chemistry, University of Illinois |
HONORS AND AWARDS
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1999: 1999: 1999: 1999: 1999: 1998: 1996: 1996: 1995: 1994: 1993: 1993: 1993: 1993: 1992: 1991: 1991: 1991: 1991: 1990: 1989: 1988: 1988: 1987-1992: 1987: 1987-1990: 1986: 1986: 1986: 1986-1987: 1985: 1983: 1983: 1980: 1980: 1974-1979: |
Doctor Honoris Causa, University of Buenos Aires, Argentina Honorary Doctor of Medicine, Uppsala University, Sweden Institute Professor, MIT The Benjamin Franklin Medal of the American Philosophical Society Honorary Doctor of Science, Thomas More College, KY Honorary Doctor of Science, University of Glasgow, Scotland Honorary Doctor of Science, Albright College, Reading, PA Honorary Doctor of Science, University of Tel Aviv Honorary Doctor of Science Degree, Bowdoin College, Brunswick, ME Honorary Doctor of Science Degree, University of Kentucky The Nobel Prize in Physiology or Medicine Elected Fellow of the American Academy of Microbiology The James R. Killian, Jr., Faculty Achievement Award, MIT The Mendel Medal Award from Villanova University, Villanova, PA The Salvador E. Luria Professorship (Chair), MIT Honorary Degree of Doctor of Humane Letters from Union College, Barbourville, KY Elected Member to the Council of the American Society for Biochemistry and Molecular Biology Elected Member of the American Philosophical Society Elected Member of the Institute of Medicine of the National Academy of Sciences The Dickson Prize, University of Pittsburgh Elected Associate Member of the European Molecular Biology Organization (EMBO) The Albert Lasker Basic Medical Research Award Louisa Gross Horwitz Prize, Columbia University The John D. MacArthur Professorship (Chair), MIT Elected Fellow of the American Association for the Advancement of Science Elected Councilor of the National Academy of Sciences The New York Academy of Sciences Award in Biological and Medical Sciences The Gairdner Foundation International Award, Canada The General Motors Research Foundation Alfred P. Sloan, Jr. Prize for Cancer Research Class of '41 Professorship (Chair), MIT The Howard Ricketts Award, The University of Chicago Elected to the National Academy of Sciences Elected to the American Academy of Arts and Sciences The Eli Lilly Award in Biological Chemistry The National Academy of Sciences' U.S. Steel Foundation Award in Molecular Biology Recipient of an American Cancer Society Career Development Award |
PROFESSIONAL SOCIETIES
The National Academy of SciencesThe American Association for the Advancement of Science
The American Society for Virology
The American Society of Biological Chemists
The American Association for Cancer Research
The American Chemical Society
The American Society for Microbiology
The American Academy of Arts and Sciences
The American Society for Biochemistry and Molecular Biology
The American Philosophical Society
EDITORIAL BOARDS
J. Virol. (to 1985); Mol. Cell. Biol. (to 1985); Virology (to 1986); Cell (to 1995); RNA (1995-)