The Secret Life of Introns

NIH Director’s Lecture | Wednesday, September 28, 2022 | 2:00 to 3:00 p.m. ET

Tracy Johnson, Ph.D.

Dean, Life Sciences; Keith and Cecilia Terasaki Presidential Endowed Chair in the Life Sciences; HHMI Professor

University of California, Los Angeles

Website

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Tracy Johnson is the Maria Rowena Ross Chair of Cell Biology and Biochemistry. Dr. Johnson moved from UC San Diego to UCLA in 2013 to join the faculty in Molecular, Cell, and Developmental Biology. She earned her B.A. in Biochemistry and Cell Biology from UCSD, her Ph.D. in Biochemistry and Molecular Biology from UC Berkeley, and was a Jane Coffin Childs postdoctoral fellow at the California Institute of Technology (Caltech) where she studied the mechanisms of RNA splicing with John Abelson. Dr. Johnson’s research is focused on the mechanisms of eukaryotic RNA processing, particularly pre-messenger RNA splicing. Her lab has most recently been interested in the coordination of these reactions with RNA synthesis and chromatin modification. Dr. Johnson is the recipient of the Presidential Early Career Award for Scientists and Engineers (PECASE) and serves on a number of scientific boards and federal Grant Review panels. In 2013, she received the UCSD Chancellor’s Associates Award for Excellence in Undergraduate Teaching and in 2013 was selected as one of the Top 20 Women Professors in California. In 2014, Dr. Johnson was named a Howard Hughes Medical Institute Professor. As one of 15 leading scientist-educators, the distinction recognizes leadership in research and education, and provides $1 million over five years to create innovative activities that integrate research with undergraduate education.

Summary

Regulation of gene expression is crucial for every function carried out by the cell, from cell growth and proliferation to the ability of the cell 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. The spliceosome undergoes dynamic and coordinated rearrangements in order to recognize splicing signals in the RNA and catalyze the splicing reaction. Remarkably, the spliceosome assembles onto the pre-mRNA co-transcriptionally, while the RNA polymerase is actively engaged with the chromatin template. This close spatial and temporal proximity of splicing and transcription raise the intriguing possibility that assembly of the spliceosome onto pre-mRNA may be influenced by transcription, and/or the state of the chromatin and vice versa; splicing may influence transcription and chromatin modification. The goal of our research is to decipher the workings of this elegant ribonucleoprotein machine. Moreover, we seek to understand how regulation of RNA splicing and other RNA processing reactions allows the cell to respond to its environment.

Lecture Objectives:

* To appreciate the unexpected roles that sequences within retained introns play in gene regulation
* To understanding why excess intron accumulation is toxic to the cell.