High-resolution RNA maps suggest common principles of splicing and 
polyadenylation regulation by TDP-43

Rot, G.; Wang, Z.; Huppertz, I.; Modic, M.; Lence, T.; Hallegger, M.; Haberman, N.; Curk, T.; von Mering, C.; Ule, J.

doi:10.1016/j.celrep.2017.04.028

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High-resolution RNA maps suggest common principles of splicing and polyadenylation regulation by TDP-43

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Huppertz, I.
Huppertz – RNA-Binding Proteins in Metabolism and Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/28467899
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Citation

Rot, G., Wang, Z., Huppertz, I., Modic, M., Lence, T., Hallegger, M., et al. (2017). High-resolution RNA maps suggest common principles of splicing and polyadenylation regulation by TDP-43. Cell Rep, 19(5), 1056-1067. doi:10.1016/j.celrep.2017.04.028.

Cite as: https://hdl.handle.net/21.11116/0000-000B-4C1A-4

Abstract

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 3' mRNA sequencing. This reveals at nucleotide resolution the "RNA maps" 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 downstream enhances 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.