High-resolution RNA maps suggest common principles of splicing and polyadenylation regulation by TDP-43
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Published version
Author(s)
Type
Journal Article
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.
Date Issued
2017-05-02
Date Acceptance
2017-04-06
Citation
Cell Reports, 2017, 19 (5), pp.1056-1067
ISSN
2211-1247
Publisher
Elsevier BV
Start Page
1056
End Page
1067
Journal / Book Title
Cell Reports
Volume
19
Issue
5
Copyright Statement
© 2017 The Author(s).
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Identifier
https://www.sciencedirect.com/science/article/pii/S2211124717305223?via%3Dihub
Subjects
0601 Biochemistry and Cell Biology
Publication Status
Published
Date Publish Online
2017-05-02