Journal
CELL REPORTS
Volume 19, Issue 5, Pages 1056-1067Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.04.028
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Funding
- European Research Council [206726-CLIP, 617837-Translate]
- Slovenian Research Agency [J7-5460]
- Swiss National Science Foundation [31003A_160095]
- Swiss National Science Foundation (SNF) [31003A_160095] Funding Source: Swiss National Science Foundation (SNF)
- The Francis Crick Institute [617837TRANSLATE] Funding Source: researchfish
- Wellcome Trust [103760/Z/14/Z] Funding Source: researchfish
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Many RNA-binding proteins (RBPs) regulate both alternative exons and poly(A) site selection. To understand their regulatory principles, we developed expressRNA, a web platform encompassing computational tools for integration of iCLIP and RNA motif analyses with RNA-seq and 30 mRNA sequencing. This reveals at nucleotide resolution the ``RNAmaps'' describing how the RNA binding positions of RBPs relate to their regulatory functions. We use this approach to examine how TDP-43, an RBP involved in several neurodegenerative diseases, binds around its regulated poly(A) sites. Binding close to the poly(A) site generally represses, whereas binding further downstreamenhances use of the site, which is similar to TDP-43 binding around regulated exons. Our RNAmotifs2 software also identifies sequence motifs that cluster together with the binding motifs of TDP-43. We conclude that TDP-43 directly regulates diverse types of pre-mRNA processing according to common position-dependent principles.
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