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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)
Verlagsversion Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 19, Heft: 5, Seiten: 1056-1067 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Stem Cell and Neuroscience
PSP-Element(e) G-552400-001
PubMed ID 28467899
DOI 10.1016/j.celrep.2017.04.028
WOS ID WOS:000402124100016
Scopus ID 85018973071
Erfassungsdatum 2017-07-05
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