Investigating BMAL1-RNA interactions and their roles in circadian rhythms

PROJECT SUMMARY The circadian clock is an endogenous timekeeping mechanism that drives daily rhythms in gene expression, physiology, and behavior. The key components of the circadian clock in mammals are transcription factors and regulators that drive rhythmic transcription. Recently, RNA has emerged as a biophysical modulator of transcription factors and other chromatin-associated factors via direct interactions. However, how these RNA- protein interactions might shape circadian rhythms remains unexplored. My preliminary data suggests that a master circadian transcription factor BMAL1 directly interacts with RNA. This led to the hypothesis that BMAL1- RNA interactions modulate circadian rhythms. To test this hypothesis, I propose the following aims: (1) Identify and characterize BMAL1-binding RNAs, (2) Define structural determinants of BMAL1-RNA interaction and determine their role in regulating circadian transcription and translation. I will carry out this study using a variety of molecular biology and genomic techniques, including a biochemical assay to capture RNA-protein interactions, RNA sequencing, and genetic manipulation. This work will uncover a novel modulatory mechanism of circadian rhythms and provide a foundation for studying the mechanistic link between the circadian clock and a wide range of RNA-mediated cellular functions. This fellowship will provide an excellent opportunity to gain expertise in molecular biology and RNA-protein interaction. This will prepare me to become an independent academic investigator studying circadian rhythms at multiple levels.