Work

Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain

Year: 2012

Type: article

Abstract: Fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43) are RNA-binding proteins pathogenetically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but it is not known if they regulate the same transcripts. We addressed this question using crosslinking and immunoprecipitation (iCLIP) in mouse brain, which showed that FUS binds along the whole length of the nascent RNA with limited sequence specificity to GGU and related motifs. A saw-tooth binding pattern in long genes demonstrated that FUS remains bound to pre-mRNAs until splicing is completed. Analysis of FUS(-/-) brain demonstrated a role for FUS in alternative splicing, with increased crosslinking of FUS in introns around the repressed exons. We did not observe a significant overlap in the RNA binding sites or the exons regulated by FUS and TDP-43. Nevertheless, we found that both proteins regulate genes that function in neuronal development.

Source: Scientific Reports

DOI: 10.1038/srep00603

Authors: Boris Rogelj, Laura E. Easton, Gireesh K. Bogu, Lawrence W. Stanton, Gregor Rot, Tomaž Curk, Blaž Zupan, Yoichiro Sugimoto, Miha Modic, Nejc Haberman, James Tollervey, Ritsuko Fujii, Toru Takumi, Christopher E. Shaw, Jernej Ule

Institutions: King's College London, MRC Laboratory of Molecular Biology, Genome Institute of Singapore, University of Ljubljana, Buck Institute for Research on Aging, Hiroshima University

Language: English

Topic: RNA Research and Splicing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690

Funders: Wellcome Trust, Ministry of Education, Culture, Sports, Science and Technology, Javna Agencija za Raziskovalno Dejavnost RS, Medical Research Council, Japan Society for the Promotion of Science, Core Research for Evolutional Science and Technology, FP7 Ideas: European Research Council

Awards: Transport in RNA vezava proteinov TDP-43 in FUS - implikacije za ALS/FTLD spekter nevrodegenerativnih bolezni (Slovene), RNA processing proteins and neurodegeneration: exploring mechanisms and modelling disease, Metode za povezovanje podatkov in znanja v sistemski biologiji mrež (Slovene), Molecular Pathogenesis of Familial Amyotrophic Lateral SclerosisType 6, RNA processing proteins and neurodegeneration: exploring mechanisms and modelling disease., Tehnologije znanj za odkrivanje novih zdravilnih učinkovin: analiza in načrtovnje eksperimentov v visokozmogljivostni genetiki (Slovene), RNA processing proteins and neurodegeneration: exploring mechanisms and modelling disease., Artificial Intelligence and Intelligent Systems, G7879866177, Modeling the transcriptome, Mapping functional protein-RNA interactions to identify new targets for oligonucleotide-based therapy.

OpenAlex ID: W2007239552

FWCI: 7.6

Cites: 52

Cited by: 271

Related to: 10