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| post-transcriptional
RNA processing as a means of gene regulation
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Sidney
Altman, Ph.D.
Sterling Professor of
Molecular, Cellular & Developmental
Biology
Email: sidney.altman@yale.edu
Room: KBT 402
Phone: (203) 432-3500/ (203) 432-3506
Fax: (203) 432-5713
B.S. M.I.T. 1960; Ph.D.
University of Colorado, Boulder 1967
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Post-transcriptional RNA processing as a means
of gene regulation is the broad subject under
investigation. This includes a genetic and biochemical
analysis of events in tRNA biosynthesis in E.
coli, yeast and human tissue. The structure of
precursor molecules, the action of specific RNases,
and, where possible, the effects of mutations
on both substrates and enzymes are all being characterized.
Our observation that M1 RNA, the RNA subunit of
RNase P from E. coli, is the catalytic subunit
of the enzyme has led to intensive investigation
of this novel enzyme. The nature of the catalytic
site and enzyme-substrate interactions are being
elucidated in biochemical studies and by making
use of the cloned gene for M1 RNA in site specific
mutagenesis studies. An investigation is underway
to determine the feasibility of using both human
and E. coli RNase P as a means to inactivate any
targeted RNA in vivo or in vitro. Particular systems
under study are drug resistance in E. coli and
influenza virus infection of mammalian cells in
tissue culture.
Studies of human RNase P have shown that two
of its seven (or more) protein subunits are antigens
that cross-react with sera of patients with autoimmune
disease. This enzyme, interestingly, is located
in the cell nucleolus along with other ribonucleoproteins.
Selected Publications
Jarrous, N., Eder, P. S., Guerrier-Takada, C.,
Hoog, C. and Altman, S. (1998) Autoantigenic Properties
of Some Protein Subunits of Catalytically Active
Complexes of Human Ribonuclease. P. RNA,
4: 407-417.
Guerrier-Takada, C., Salavati, R. and Altman,
S. (1997) Phenotypic conversion of drug-resistant
bacteria to drug sensitivity. Proc. Nat. Acad.
Sci. USA, 94: 8468-8472.
Plehn-Dujowich, D. and Altman, S. (1998) Effective
inhibition of influenza virus production in cultured
cells by external guide sequences and RNase P.
Proc. Nat. Acad. Sci. USA, 95: 7327-7332.
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