post-transcriptional RNA processing as a means of gene regulation
	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

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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