SPONSORED BY: Lexogen
Jernej Ule, PhD
Group Leader, The Francis Crick Institute
Gregor Rot, PhD
Postdoctoral Researcher, Institute of Molecular Life Sciences University of Zurich
Many RNA binding proteins (RBPs) regulate the selection of alternative polyA sites. To understand their regulatory principles, we developed expressRNA, a web platform encompassing computational tools for integration of the QuantSeq 3´ mRNA-Seq, iCLIP and RNA motif analyses. This reveals at nucleotide resolution the ‘RNA maps’, which demonstrate that RBPs bind to specific positions on pre-mRNAs to regulate the polyA sites. Our RNAmotifs2 software also identifies clustered sequence motifs that mediate the regulation of these sites. We used this approach to show that TDP-43, an RBP involved in several neurodegenerative diseases, binds close to the polyA site to repress, and further downstream to enhance their use. We conclude that TDP 43 directly regulates diverse types of pre-mRNA processing events according to common positional principles.
- How to analyse 3´ mRNA-Seq QuantSeq data
- How to use the expressRNA platform
- Why is it helpful to derive an RNA map, and what does it show us about regulatory mechanisms?