Mechanisms and regulation of gene expression Our laboratory studies several aspects of gene expression in animal cells. These include transcription of mRNA encoding genes, mRNA splicing, and mRNA polyadenylation. All three of these processes occur in the cell nucleus and require numerous protein (and in the case of splicing, RNA) factors that assemble into massive multi-subunit complexes. It is our goal to understand how the complexes assemble and function on the DNA template or pre-mRNA substrate, and to learn how these important molecules act to regulate gene expression and how they themselves are controlled. These studies involve a large number of experimental approaches, including a variety of in vitro assays, biochemical fractionation and protein purification, cDNA and genomic DNA cloning, production of recombinant proteins and antibodies, in vitro mutagenesis, and genetic analyses using a variety gene targeting approaches.
| 1971 |
B.S. Columbia University |
| 1976 |
Ph. D. State University of New York, Stony Brook, NY |
| 1976 |
Anna Fuller Fellowship |
| 1990 |
Brockman Memorial Lecture, University of Michigan |
| 1996- |
NIH MERIT Award (mRNA splicing) |
| 1998 |
ASBMB- Plenary Lecturer |
| 2002 |
American Academy of Microbiology (elected) |
| 2005- |
ISI Highly Cited Researcher |
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| 1983-1985 |
Editorial Board, Nucleic Acids Research |
| 1984-2001 |
Editorial Board, Molecular Cell Biology |
| 1988- |
Editorial Board, Genes and Development |
| 1989-1992 |
Editorial Board, Techniques |
| 1991-1995 |
Editorial Board, Mechanisms of Development |
| 1991- |
Associate Editor, Gene Expression |
| 1993-1998 |
Editorial Board, Journal of Virology |
| 1994- |
Editorial Board, RNA |
| 1997- |
Editorial Board, Molecular Cell |
| 2001- |
Editorial Advisor, BioMedCentral-Mol. Biol |
| 2003- |
Editor, Molecular Cell Biology |
| 2003- |
Editorial Board, BioMedCentral-Biology |
- Kashima, T. and Manley, J.L. (2003). A negative element in SMN2 exon 7 inhibits splicing in Spinal Muscular Atrophy. Nature Genetics 34, 460-463.
- Xu, Y., Hirose, Y., Zhou, X., Lu, K.P. and Manley, J.L. (2003). Pin1 modulates the structure and function of RNA polymerase II. Genes Dev. 17, 2765-2776.
- Shin, C., Feng, Y. and Manley, J.L. (2004). Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock. Nature 427, 553-558.
- Kleiman, F.E., Wu-Baer, F., Kaneko, S., Baer, R. and Manley, J.L. (2005). BRCA1/BARD1 inhibition of 3' processing involves targeted degradation of RNA polymerase II. Genes Dev. 19, 1227-1237.
- Li, X. and Manley, J.L. (2005). Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. Cell 122, 365-78.
- Li, X., Wang, J. Kashima, T. and Manley, J.L. (2005). Loss of splicing factor ASF/SF2 induces cell- cycle arrest and apoptosis, but inhibits internucleosomal DNA fragmentation. Genes Dev.
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