RNA plays an important role in regulating cellular gene expression. Its ability to fold into secondary and tertiary structures underlies the RNA’s ability to function and be processed in every step of its life cycle, including transcription, splicing, cellular localization, translation and turnover of the RNA. However, structural information for most RNAs in the cells, such as mRNAs, is missing due to the low throughput nature of RNA structure probing and the traditional difficulty of probing long RNAs, making it difficult to assess the full impact of RNA structure in biology. To fulfill the need to understand the roles of RNA structure on a global scale, we developed for the first time a novel strategy termed Parallel Analysis of RNA Structure (PARS), which couples structure-specific probing to high throughput sequencing to simultaneously generate secondary structures for thousands of RNA species at single nucleotide resolution. Applying PARS to the yeast transcriptome identified distinct structural organization of mRNAs, including a three nucleotide periodicity in the coding region and increased accessibility near the start codon for translation. Furthermore, we demonstrated that PARS can be used to study dynamics by probing the yeast transcriptome across a temperature gradient to identify functional structural regions that have differential propensity to melt. PARS can be readily applied to different organisms and conditions, to identify structural determinants that regulate gene expression changes across organisms in different cellular states. This expansion of RNA structural data will likely enhance our understanding of how RNA structure translates into RNA function in cellular systems, as well as open doors to potentially targeting these structural elements to regulate cellular behavior in diseases.

Biography

Yue Wan was awarded the NSS-PhD scholarship from A*STAR in 2003. She obtained her B.Sc in Cell Biology and Biochemistry from the University of California, San Diego in 2006. She is currently a PhD student in the Cancer Biology program at Stanford University, California, USA, under the mentorship of Howard Y. Chang. During her PhD, she developed a high-throughput method for probing RNA structures genome-wide and is interested in understanding how RNA structures impact cellular biology.

Host: Prof. Uttam Surana