Rot, G;
Wang, Z;
Huppertz, I;
Modic, M;
Lence, T;
Hallegger, M;
Haberman, N;
... Ule, J; + view all
(2017)
High-Resolution RNA Maps Suggest Common Principles of Splicing and Polyadenylation Regulation by TDP-43.
Cell Reports
, 19
(5)
pp. 1056-1067.
10.1016/j.celrep.2017.04.028.
Preview |
Text
Ule_1-s2.0-S2211124717305223-main.pdf - Published Version Download (2MB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | High-Resolution RNA Maps Suggest Common Principles of Splicing and Polyadenylation Regulation by TDP-43 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2017.04.028 |
| Publisher version: | http://doi.org/10.1016/j.celrep.2017.04.028 |
| Language: | English |
| Additional information: | 7 ª 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/). |
| Keywords: | alternative polyadenylation; TDP-43; RNA map; positional regulatory principles; clustered sequence motifs; alternative splicing; expressRNA; RNAmotifs2; 3′ mRNA sequencing; iCLIP |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1555381 |
Archive Staff Only
 |
View Item |
