- Craig Kaplan
- Associate Professor
- Biochemistry 322A
- Undergraduate Education
- BS in Biology, Latin Language and Literature, University of Michigan, 1995
- Graduate Education
- Ph.D. Harvard University, 2003
- 2014 Dean's Outstanding Achievement Award for Early Career Research
- Courses Taught
- BICH/GENE 431 Molecular Genetics
- BICH 681 Scientific Communication
Overview of Kaplan Lab research: Mechanism and regulation of transcription by RNA Polymerase II
Control of gene expression in eukaryotes relies on complex regulatory machinery dedicated to proper transcription by RNA Polymerase II (Pol II). My lab focuses on the mechanism and regulation of Pol II enzymatic activity and how it can impact all three phases of transcription: initiation, elongation, and termination. Appropriate regulation of transcription is critical for cellular and organismal development, and is also essential for the prevention of disease states such as cancer. We study Pol II regulation using the model organism, Saccharomyces cerevisiae (Baker’s yeast). This single-celled organism is amenable to genetic, biochemical, genomic and high-throughput approaches, thus we are able to approach mechanism in vivo and in vitro.
One goal of my lab is determining the roles and mechanisms of transcription elongation factors that directly impact Pol II activity, as well as those that coordinate Pol II activity with other co-transcriptional processes, such as RNA processing or epigenetic marking of the chromatin template in vivo. We have taken a genome-scale high-throughput genetic approach for the identification of such factors. Additionally, we are interested in the basic mechanism of Pol II substrate selection and how it may be compromised by natural products such as the mushroom toxin alpha-amanitin. Substrate selection is a key determinant for proper elongation rate and faithful transcription, while molecules that alter or inhibit substrate selection could represent novel classes of anti-fungal or therapeutic drugs.
Control of transcription start site selection by RNA polymerase II
A major interest in the Kaplan lab are the mechanisms by which transcription starts sites (TSSs) are specified in Pol II transcription. In the budding yeast S. cerevisiae, a scanning mechanisms operates whereby Pol II surveys sequence in the start region in an upstream to downstream fashion (relative to the direction of transcription). This process is sensitive to Pol II catalytic efficiency and can be influenced by DNA sequence. What are the rules and how does initiation interface with chromatin structure? How are scanning and initiation coupled and uncoupled?
Malik, I, Qiu, C, Snavely, T, Kaplan, CD. Wide-ranging and unexpected consequences of altered Pol II catalytic activity in vivo. Nucleic Acids Res. 2017; :.
Qiu, C, Erinne, OC, Dave, JM, Cui, P, Jin, H, Muthukrishnan, N et al.. High-Resolution Phenotypic Landscape of the RNA Polymerase II Trigger Loop. PLoS Genet. 2016;12 (11):e1006321.
Kaplan, CD. Pairs of promoter pairs in a web of transcription. Nat. Genet. 2016;48 (9):975-6.
Bird, JG, Zhang, Y, Tian, Y, Panova, N, Barvík, I, Greene, L et al.. The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA. Nature. 2016;535 (7612):444-7.
Cui, P, Jin, H, Vutukuru, MR, Kaplan, CD. Relationships Between RNA Polymerase II Activity and Spt Elongation Factors to Spt- Phenotype and Growth in Saccharomyces cerevisiae. G3 (Bethesda). 2016;6 (8):2489-504.
Kaster, BC, Knippa, KC, Kaplan, CD, Peterson, DO. RNA Polymerase II Trigger Loop Mobility: INDIRECT EFFECTS OF Rpb9. J. Biol. Chem. 2016;291 (28):14883-95.
Barnes, CO, Calero, M, Malik, I, Graham, BW, Spahr, H, Lin, G et al.. Crystal Structure of a Transcribing RNA Polymerase II Complex Reveals a Complete Transcription Bubble. Mol. Cell. 2015;59 (2):258-69.
Murakami, K, Mattei, PJ, Davis, RE, Jin, H, Kaplan, CD, Kornberg, RD et al.. Uncoupling Promoter Opening from Start-Site Scanning. Mol. Cell. 2015;59 (1):133-8.
Jeronimo, C, Watanabe, S, Kaplan, CD, Peterson, CL, Robert, F. The Histone Chaperones FACT and Spt6 Restrict H2A.Z from Intragenic Locations. Mol. Cell. 2015;58 (6):1113-23.
Čabart, P, Jin, H, Li, L, Kaplan, CD. Activation and reactivation of the RNA polymerase II trigger loop for intrinsic RNA cleavage and catalysis. Transcription. 2014;5 (3):e28869.