BioE Seminar Series: Tracy Johnson, PhD
Thursday, September 16, 2021
12:00 pm - 1:00 pm
Tracy Johnson, PhD, Keith and Cecilia Terasaki Presidential Endowed Chair in Life Sciences, Professor of Molecular, Cell, and Developmental Biology, HHMI Professor, University of California-Los Angeles
Regulation of gene expression is crucial for every function carried out by the cell-from cell growth and proliferation to the cell's ability to respond to its ever-changing environment. Hence, understanding cellular function and dysfunction is dependent upon deciphering these gene regulatory mechanisms. This is particularly challenging in the case of eukaryotic genes, which are often interrupted by long stretches of noncoding sequences (introns). These are removed from the newly synthesized RNA, and the remaining sequences (exons) are ligated together to form a mature messenger RNA. This process, pre-messenger RNA splicing, is carried out by the spliceosome made up of 5 small nuclear RNAs and over 100 proteins. Correct splicing is crucial to proper gene expression. In fact, it is estimated that over a quarter of all point mutations that lead to genetic disease are caused by defective splicing. The spliceosome undergoes dynamic rearrangements in order to recognize splicing signals in the RNA and catalyze the splicing reaction. The goal of our research is to decipher the workings of this elegant ribonucleoprotein "machine," which has become even more intriguing in light of evidence that splicing signals are recognized co-transcriptionally, while the RNA polymerase is still engaged with a chromatin template. Our work is focused on three key areas (i) understanding the molecular details of the spliceosome rearrangements involved in splice site recognition and splicing catalysis; (ii) dissecting how this occurs in the context of transcription, chromatin modification, and other RNA processing events; and (iii) understanding how the cell exploits these mechanisms to respond to its environment.