Jeff Pleiss received his B.A. in Chemistry at Northwestern University where he worked with Tobin Marks in the field of organometallic chemistry. Jeff's graduate work was completed in the lab of Olke Uhlenbeck at the University of Colorado, Boulder where he learned biochemical and biophysical techniques for studying the biology of RNA. Jeff was then supported as a fellow of the Damon Runyon Cancer Research Foundation for his work in Christine Guthrie's lab at the University of California, San Francisco. Here, Jeff combined the power of yeast genetics with nascent genomics tools to examine mechanisms by which RNA processing can function to regulate gene expression. In 2007 Jeff joined the Department of Molecular Biology and Genetics at Cornell University, where he combines biochemistry, biophysics, molecular biology, genetics, and high-throughput genomics to elucidate pathways in RNA biology that are critical for eukaryotic gene expression. Jeff's work is funded by the National Institutes of Health and the American Cancer Society.
Pre-mRNA splicing is an essential component of eukaryotic gene expression. Many metazoans, including humans, regulate alternative splicing patterns to generate expansions of their proteome from a limited number of genes. Importantly, a considerable fraction of human disease causing mutations manifest themselves through altering the sequences that shape the splicing patterns of genes. Nevertheless, the mechanisms by which this complex pathway is regulated remain poorly understood. Understanding how disease-causing mutations impair this ability will require improved knowledge of the mechanisms by which the spliceosome identifies and activates ‘cognate’ splice site sequences in the background of scores of ‘near-cognate’ aberrant splice sites: understanding this problem is a major focus of the work in the Pleiss lab.
In the Pleiss lab, we develop and utilize novel genetic, genomic, computational, molecular biological, and comparative evolutionary approaches geared towards understanding both the mechanistic bases of splicing regulation as well as its physiological consequences. At the simplest level, this requires understanding both: (1) the cis-regulatory elements within a transcript (or gene structure) that destine it for regulation; and (2) the mechanistic bases by which trans-regulatory factors can impart this specific regulation. Work in my lab largely focuses on addressing these questions using the budding and fission yeasts, S. cerevisiae and S. pombe. Whereas budding yeast has long been a powerful genetic system for understanding the basic mechanisms of splicing, my lab has pioneered global studies of splicing in S. pombe, an organism which has retained many features of mammalian splicing, including degenerate splice site sequences, the presence of SR-proteins, and the usage of exonic splicing enhancers, yet retains the genetic tractability of budding yeast.
- Das, J., Vo, T. V., Wei, X., Mellor, J. C., Tong, V., Degatano, A. G., Wang, X., Wang, L., Cordero, N. A., Kruer-Zerhusen, N., Matsuyama, A., Pleiss, J. A., Lipkin, S. M., Yoshida, M., Roth, F. P., & Yu, H. (2013). Cross-species protein interactome mapping reveals species-specific wiring of stress response pathways. Science Signaling. 6.
- Cui, J., Sartain, C. V., Pleiss, J. A., & Wolfner, M. F. (2013). Cytoplasmic polyadenylation is a major mRNA regulator during oogenesis and egg activation in Drosophila. Developmental Biology. 383:121-131.
- Awan, A., Manfredo, A., & Pleiss, J. A. (2013). Lariat Sequencing in a Unicellular Yeast Identifies Regulated Alternative Splicing of Exons that are Evolutionarily Conserved with Humans. PNAS: Proceedings of the National Academy of Sciences of the United States of America. 110:12762-12767.
- Albulescu, L., Sabet, N., Gudipati, M., Stepankiw, N., Bergman, Z., Huffaker, T. C., & Pleiss, J. A. (2012). A Quantitative, High-Throughput Reverse Genetic Screen Reveals Novel Connections Between pre-mRNA Splicing and 5' and 3'-End Transcript Determinants. PLOS Genetics. 8:e1002530.
- Weiner, A., Chen, H. V., Liu, C. L., Rahat, A., Klien, A., Soares, L., Gudipati, M., Pfeffner, J., Regev, A., Buratowski, S., Pleiss, J. A., Friedman, N., & Rando, O. J. (2012). Systematic dissection of roles for chromatin regulators in a yeast stress response. PLOS Biology. 10:e1001369.
- Abelson, J., Blanco, M., Ditzler, M. A., Fuller, F., Aravamudhan, P., Wood, M., Villa, T., Ryan, D. E., Pleiss, J. A., Maeder, C., Guthrie, C., & Walter, N. G. (2010). Conformational dynamics of single pre-mRNA molecules during in vitro splicing. Nature Structural & Molecular Biology. 17:504-512.
- Inada, M., & Pleiss, J. A. (2010). Genome-wide approaches to monitor pre-mRNA splicing. Methods in Enzymology. 470:51-75.
- Zhang, L., Xu, T., Maeder, C., Bud, L., Shanks, J., Nix, J., Guthrie, C., Pleiss, J. A., & Zhao, R. (2009). Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2. Nature Structural & Molecular Biology. 16:731-739.
- Pleiss, J. A., Whitworth, G., Bergkessel, M., & Guthrie, C. (2007). Rapid, transcript-specific changes in splicing in response to environmental stress. Molecular Cell. 27:928-937.
- Pleiss, J. A., Whitworth, G., Bergkessel, M., & Guthrie, C. (2007). Transcript-specificity in Yeast pre-mRNA Splicing Revealed by Mutations in Core Spliceosomal Components. PLOS Biology. 5:e90.