James P. Bruzik, Ph.D.

Associate Professor

Center for RNA Molecular Biology

Curriculum Vitae

Research: Regulation of alternative pre-mRNA splicing

Our lab investigates the mechanism of alternative pre-mRNA splicing in mammalian cells. We have demonstrated that neither the U1 nor the U2 snRNP is recruited to activated 5' splice sites through the use of an M2S-RS fusion protein-dependent splicing substrate. Rather, our results point to the possibility that the U4/6-5 tri-snRNP is the recruited factor. Currently, we are testing the hypothesis that the tri-snRNP is recruited to alternative 5' splice sites via the interaction of RS domain-containing proteins. This data is very interesting because we have demonstrated that alternative 5' splice sites appear to be activated later in the spliceosome assembly pathway than had previously been thought. In addition, we have initiated an investigation of the mechanism of alternative splicing of the Bcl-x gene. The Bcl-x pre-mRNA contains alternative 5' splice sites whose utilization leads to long and short mRNA products. These mRNAs display opposite activities in the apoptotic pathway. We will investigate the regulation of alternative 5' splice site utilization in the Bcl-x pre-mRNA and relate our results to the mechanistic insights that we have gained from the study of alternative 5' splice sites described above. Finally, we have initiated a collaboration with Dr. Xiang-Dong Fu (UCSD) to study the coordinated regulation of alternative pre-mRNA splicing in prostate cancer. Dr. Fu has identified a panel of pre-mRNA substrates via microarray analysis, that undergo alternative splicing in prostate cancer. We will examine these splicing events at the mechanistic level in order to determine whether alternative splicing of the identified targets is effected by common regulatory pathways.

More Information

Selected Publications

L. A. Boukis, N. Liu, S. Furuyama and J.P. Bruzik (2004)
Ser/Arg-rich protein-mediated communication between U1 and U2 small nuclear ribonucleoprotein particles.
J. Biol. Chem. 279, 29647-29653. /

S. Furuyama and J.P. Bruzik (2003)
Trans-splicing
In D.N. Cooper (ed.)
Encyclopedia of the Human Genome 5, 623-628. Nature Publishing Group, London. /

S. Furuyama and J.P. Bruzik (2002)
Multiple roles for SR proteins in trans-splicing.
Mol. Cell. Biol. 22, 5337-5346. /

J.R. Sanford and J.P. Bruzik (2001)
Regulation of SR protein localization during development.
Proc. Natl. Acad. Sci. USA. 98, 10184-10189. /

L. A. Boukis and J.P. Bruzik (2001)
Functional selection of splicing enhancers that activate trans-splicing in vitro.
RNA 7, 793-805. /

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