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001-es BibID:BIBFORM037635
Első szerző:Tollervey, James R.
Cím:Characterizing the RNA targets and position-dependent splicing regulation by TDP-43 / Tollervey James R., Curk Tomaz, Rogelj Boris, Briese Michael, Cereda Matteo, Kayikci Melis, König Julian, Hortobágyi Tibor, Nishimura Agnes L., Zupunski Vera, Patani Rickie, Chandran Siddharthan, Rot Gregor, Zupan Blaz, Shaw Christopher E., Ule Jernej
Dátum:2011
ISSN:1097-6256
Megjegyzések: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.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Nature Neuroscience. - 14 : 4 (2011), p. 452-458. -
További szerzők:Curk, Tomaž Rogelj, Boris Briese, Michael Cereda, Matteo Kayikci, Melis König, Julian Hortobágyi Tibor (1965-) (patológus) Nishimura, Agnes Lumi Župunski, Vera Patani, Rickie Chandran, Siddharthan Rot, Gregor Zupan, Blaž Shaw, Christopher E. Ule, Jernej
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