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

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

Cell Rep. 19, 1056-1067 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 3′ Mrna Sequencing ; Rna Map ; Rnamotifs2 ; Tdp-43 ; Alternative Polyadenylation ; Alternative Splicing ; Clustered Sequence Motifs ; Expressrna ; Iclip ; Positional Regulatory Principles; Cleavage Factor-i; 3' Utr Length; Alternative Polyadenylation; Binding Proteins; Global Analyses; Prediction; Sequences; Insights; Reveals; Genes
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 19, Issue: 5, Pages: 1056-1067 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)