Department of Biochemistry
Title: Dynamic regulation of gene expression by long non-coding RNAs
Abstract: Long non-coding (lnc)RNAs, once thought to merely represent noise from imprecise transcription initiation, have now emerged as major regulatory entities of gene expression in all eukaryotes. Major efforts are now being put forth to identify the mechanism(s) of action for individual lncRNAs. Using the budding yeast S. cerevisiae as a model, we found that lncRNAs associated with galactose (GAL) cluster genes promote gene induction from a prior, transcriptionally repressed state. Rapid induction involves formation of lncRNA-DNA hybrids or R-loops across the GAL cluster, which form transiently upon nuclear export of RNA helicase Dbp2, and disrupt binding of promoter-associated transcriptional repressors. Interestingly, the GAL lncRNAs enhance the kinetics of transcriptional induction within a population of yeast cells, without effecting the final levels of the protein coding genes. We suggest that the GAL lncRNAs poise inducible genes for rapid activation; enabling cells to more effectively trigger new transcriptional programs in response to cellular cues. Consistently, the GAL lncRNAs confer a competitive fitness advantage to yeast cells over those lacking lncRNA expression. Ongoing work to understand the broader role of R-loops in lncRNA-dependent gene regulation will be discussed.