Join us for MLS Seminar featuring Dr. Athma Pai, Associate Professor of at the UMass Chan Medical School! The title of her talk is Noise to Signal: Studying the Efficiency of mRNA Processing.
It is becoming increasingly clear that alternative mRNA processing is a major factor underlying human phenotypes, disease etiology, and cellular responses to external stimuli. Though we have begun to unravel the genetic factors involved in regulating alternative isoform usage, we do not yet understand the temporal dynamics of RNA processing decisions. The development of high-throughput sequencing approaches to systematically capture and analyze nascent pre-mRNA molecules at defined time-scales has opened the door for genome-wide kinetic profiling of RNA maturation. Many steps of RNA maturation – including mRNA splicing and cleavage – are thought to occur primarily co-transcriptionally, with substantial interplay between the rate of transcription elongation and choices involved in isoform variability. Furthermore, there is increasing evidence that these steps are often co-regulated to ensure expression of precise full length isoforms. Thus, measuring the speed, accuracy, and coordination of mRNA processing decisions is central to understanding the regulation of initial gene regulatory decisions and mRNA biogenesis. Previous methods to do so have imaged single loci, studied dynamics in mutated or heavily altered genes, or used chemical treatments that affect cellular metabolisms. I will describe our ongoing development and application of computational genomics approaches to estimate genome-wide kinetics, fidelity, and coupling of transcription elongation, mRNA splicing, and mRNA cleavage decisions in eukaryotic cells.
