ePrints.FRI - University of Ljubljana, Faculty of Computer and Information Science

Characterizing the RNA targets and position-dependent splicing regulation by TDP-43

James R Tollervey and Tomaz Curk and Boris Rogelj and Michael Briese and Matteo Cereda and Melis Kayikci and Julian Konig and Tibor Hortobágyi and Agnes L Nishimura and Vera Zupunski and Rickie Patani and Siddharthan Chandran and Gregor Rot and Blaz Zupan and Christopher E Shaw and Jernej Ule (2011) Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nature Neuroscience, 14 (4). pp. 452-458.

Full text not available from this repository.


TDP-43 is a predominantly nuclear RNA-binding protein that forms inclusion bodies in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The mRNA targets of TDP-43 in the human brain and its role in RNA processing are largely unknown. Using individual nucleotide-resolution ultraviolet cross-linking and immunoprecipitation (iCLIP), we found that TDP-43 preferentially bound long clusters of UG-rich sequences in vivo. Analysis of RNA binding by TDP-43 in brains from subjects with FTLD revealed that the greatest increases in binding were to the MALAT1 and NEAT1 noncoding RNAs. We also found that binding of TDP-43 to pre-mRNAs influenced alternative splicing in a similar position-dependent manner to Nova proteins. In addition, we identified unusually long clusters of TDP-43 binding at deep intronic positions downstream of silenced exons. A substantial proportion of alternative mRNA isoforms regulated by TDP-43 encode proteins that regulate neuronal development or have been implicated in neurological diseases, highlighting the importance of TDP-43 for the regulation of splicing in the brain.

Item Type: Article
Keywords: TDP-43, RNA targets
Related URLs:
http://www.cobiss.si/scripts/cobiss?command=search&base=50070&select=(id=8278100)Alternative location
Institution: University of Ljubljana
Department: Faculty of Computer and Information Science
Divisions: Faculty of Computer and Information Science > Bioinformatics Laboratory
Item ID: 1478
Date Deposited: 22 Jul 2011 13:37
Last Modified: 02 Dec 2013 14:15
URI: http://eprints.fri.uni-lj.si/id/eprint/1478

Actions (login required)

View Item