Extracting in vivo mRNA processing rates from RNA sequencing data

25 June 2010

Michael Springer
Department of Systems Biology
Harvard Medical School

Abstract

The prevailing view of pre-mRNA processing is that splicing occurs co-transcriptionally, taking place soon after each intron is synthesized. These conclusions are based on the association of splicing machinery with RNA polymerases and the observation of co-transcriptional splicing at a select few genes. The actual in vivo rates of RNA processing versus transcription and the extent to which these rates vary across a whole metazoan genome is unclear. We have performed RNA sequencing (RNA-Seq) of total RNA from mouse and human cells to assess pre-mRNA processing globally. The density of RNA-Seq reads across annotated genes provides quantitative information about the expression levels of different features of a single RNA (eg: exons, introns and the junctions between them). Even though we make a single steady-state measurement, we are able to extract rates constant for splicing, intron degredation and mRNA turn-over with the aid of a simple model for RNA processing.

This will be a joint theory lunch with David Harmin and Jesse Gray.

current theory lunch schedule