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)
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
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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
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Language
english
Publication Year
2017
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2017
ISSN (print) / ISBN
2211-1247
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2211-1247
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Volume: 19,
Issue: 5,
Pages: 1056-1067
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Cell Press
Publishing Place
Cambridge
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Peer reviewed
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Stem Cell and Neuroscience
PSP Element(s)
G-552400-001
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Erfassungsdatum
2017-07-05