Niroshika Keppetipola

Determining the role of chemical modifications in RNA binding protein function

An important way that cells respond to environment is by controlling gene expression and in turn protein expression. The splicing of mRNA intermediates is an important mechanism for cells to regulate protein expression and in turn control development and respond to changes in the environment. RNA binding proteins play an important role in controlling the process of splicing and in turn regulating the protein composition of the cell. Many of these RNA binding proteins occur as gene families with members sharing high primary and tertiary structure similarity but have distinct tissue-specific expression patterns. Moreover, members regulate overlapping and distinct sets of target exons to elicit tissue-specific gene expression patterns. How highly structurally similar proteins can regulate distinct splicing outcomes is not well understood.

Recent studies highlight that many of these RNA binding proteins are modified by the addition of chemical groups such as acetate and phosphate. Thus, it is likely that these post-translational modifications play a role in RNA binding protein function and in turn in tissue-specific gene expression. Studies conducted in the lab aim to test this hypothesis.

Selected publications (Click for full list)

Truong, A., Barton, M., Tran, U., Mellody, M., Berger, D., Madory, D., . . . Keppetipola, N. (2024). Unstructured linker regions play a role in the differential splicing activities of paralogous RNA binding proteins PTBP1 and PTBP2. J Biol Chem, 105733. doi:10.1016/j.jbc.2024.105733

Pina, J. M., Hernandez, L. A., & Keppetipola, N. M. (2022). Polypyrimidine tract binding proteins PTBP1 and PTBP2 interact with distinct proteins under splicing conditions. PLoS One, 17(2), e0263287. doi:10.1371/journal.pone.0263287

Pimentel, C., Le, C., Tuttobene, M. R., Subils, T., Martinez, J., Sieira, R., . . . Ramirez, M. S. (2021). Human Pleural Fluid and Human Serum Albumin Modulate the Behavior of a Hypervirulent and Multidrug-Resistant (MDR) Acinetobacter baumannii Representative Strain. Pathogens, 10(4). doi:10.3390/pathogens10040471

Keppetipola, N., & Patchen, T. (2021). Titrating Teaching: An Interdisciplinary Case Study of Online and Face-to-Face Undergraduate Biochemistry Instruction. J Microbiol Biol Educ, 22(1). doi:10.1128/jmbe.v22i1.2603

Ontiveros, R. J., Hernandez, L., Nguyen, H., Hernandez Lopez, A. L., Shankar, A., Kim, E., & Keppetipola, N. M. (2020). Identification and Characterization of a Minimal Functional Splicing Regulatory Protein, PTBP1. Biochemistry, 59(50), 4766-4774. doi:10.1021/acs.biochem.0c00664

Pina, J. M., Reynaga, J. M., Truong, A. A. M., & Keppetipola, N. M. (2018). Post-Translational Modifications in Polypyrimidine Tract Binding Proteins PTBP1 and PTBP2. Biochemistry, 57(26), 3873-3882. doi:10.1021/acs.biochem.8b00256

Martinez, A. A., Espinosa, B. A., Adamek, R. N., Thomas, B. A., Chau, J., Gonzalez, E., . . . Salzameda, N. T. (2018). Breathing new life into West Nile virus therapeutics; discovery and study of zafirlukast as an NS2B-NS3 protease inhibitor. Eur J Med Chem, 157, 1202-1213. doi:10.1016/j.ejmech.2018.08.077