dc.contributor.author | Tollervey, JR | |
dc.contributor.author | Curk, T | |
dc.contributor.author | Rogelj, B | |
dc.contributor.author | Briese, M | |
dc.contributor.author | Cereda, M | |
dc.contributor.author | Kayikci, M | |
dc.contributor.author | König, J | |
dc.contributor.author | Hortobágyi, T | |
dc.contributor.author | Nishimura, AL | |
dc.contributor.author | Zupunski, V | |
dc.contributor.author | Patani, R | |
dc.contributor.author | Chandran, S | |
dc.contributor.author | Rot, G | |
dc.contributor.author | Zupan, B | |
dc.contributor.author | Shaw, CE | |
dc.contributor.author | Ule, J | |
dc.date.accessioned | 2024-01-04T12:27:04Z | |
dc.date.available | 2011-02-02 | |
dc.date.available | 2024-01-04T12:27:04Z | |
dc.date.issued | 2011-02-27 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/93368 | |
dc.description.abstract | 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. | en_US |
dc.format.extent | 452 - 458 | |
dc.language | eng | |
dc.publisher | Nature Research | en_US |
dc.relation.ispartof | Nat Neurosci | |
dc.subject | Alternative Splicing | en_US |
dc.subject | Brain Chemistry | en_US |
dc.subject | Cell Line | en_US |
dc.subject | Cell Line, Tumor | en_US |
dc.subject | DNA-Binding Proteins | en_US |
dc.subject | Gene Expression Regulation | en_US |
dc.subject | Humans | en_US |
dc.subject | Protein Isoforms | en_US |
dc.subject | RNA Splicing | en_US |
dc.subject | RNA, Messenger | en_US |
dc.subject | RNA, Untranslated | en_US |
dc.subject | RNA-Binding Proteins | en_US |
dc.title | Characterizing the RNA targets and position-dependent splicing regulation by TDP-43 | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1038/nn.2778 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/21358640 | en_US |
pubs.issue | 4 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 14 | en_US |
dcterms.dateAccepted | 2011-02-02 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |