title: Position-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions.
abstract: FUS is an RNA-binding protein that regulates transcription, alternative splicing, and mRNA transport. Aberrations of FUS are causally associated with familial and sporadic ALS/FTLD. We analyzed FUS-mediated transcriptions and alternative splicing events in mouse primary cortical neurons using exon arrays. We also characterized FUS-binding RNA sites in the mouse cerebrum with HITS-CLIP. We found that FUS-binding sites tend to form stable secondary structures. Analysis of position-dependence of FUS-binding sites disclosed scattered binding of FUS to and around the alternatively spliced exons including those associated with neurodegeneration such as Mapt, Camk2a, and Fmr1. We also found that FUS is often bound to the antisense RNA strand at the promoter regions. Global analysis of these FUS-tags and the expression profiles disclosed that binding of FUS to the promoter antisense strand downregulates transcriptions of the coding strand. Our analysis revealed that FUS regulates alternative splicing events and transcriptions in a position-dependent manner.
authors: Department of Neurology, Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Shinsuke
authors: S
authors: Ishigaki
authors: Akio
authors: A
authors: Masuda
authors: Yusuke
authors: Y
authors: Fujioka
authors: Yohei
authors: Y
authors: Iguchi
authors: Masahisa
authors: M
authors: Katsuno
authors: Akihide
authors: A
authors: Shibata
authors: Fumihiko
authors: F
authors: Urano
authors: Gen
authors: G
authors: Sobue
authors: Kinji
authors: K
authors: Ohno
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002525:Cerebellar Cortex / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D051379:Mice; D058977:Molecular Sequence Annotation; D009046:Motor Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D034702:RNA-Binding Protein FUS; D012313:RNA