Viral Noncoding RNAs: Approaching Answers

Wednesday, September 23, 2020 | 3:00 to 4:00 p.m. ET

Joan A. Steitz, Ph.D.

Sterling Professor of Molecular Biophysics and Biochemistry

Yale University

Steitz is best known for her pioneering work in RNA. She and her student Michael Lerner discovered and defined the function of small ribonucleoproteins (snRNPs) in pre-messenger RNA—the earliest product of DNA transcription—and was the first to learn that these cellular complexes (snRNPs) play a key role in processing messenger RNA by excising noncoding regions and splicing together the resulting segments. Her breakthroughs into the previously mysterious splicing process have clarified the science behind the formation of proteins and other biological processes, including the intricate changes that occur as the immune system and brain develop. Steitz earned her Ph.D. from Harvard in 1967. After completing postdoctoral work in Cambridge, England, she joined the Department of Molecular Biophysics and Biochemistry at Yale as an assistant professor and later became an associate and full professor, as well as chair of the department.

Summary

Noncoding (nc)RNAs play pivotal roles in the regulation of gene expression, but exhibit a diversity of functions whether encoded by cellular or viral genomes. One such ncRNA expressed in cells infected by the oncogenic gamma herpesvirus KSHV is the highly abundant polyadenylated nuclear (PAN) RNA, which is required for production and release of new virus particles. Our studies of PAN RNA uncovered the existence of RNA elements called ENEs, which stabilize transcripts by engaging the polyA tail or 3’-terminal A-rich tract in a triple-helical RNA structure that obstructs the initiation of degradation. Structural analyses of ENEs from the PAN ncRNA, from the vertebrate long ncRNA MALAT1 and recently from double ENEs complexed with polyA have led to unanticipated identification of novel polyA tail interactions that are important for stabilizing RNAs inside cells. The most recent high-resolution X-ray structures will be discussed.