Position-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions

Shinsuke Ishigaki, Akio Masuda, Yusuke Fujioka, Yohei Iguchi, Masahisa Katsuno, Akihide Shibata, Fumihiko Urano, Gen Sobue, Kinji Ohno

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122 Scopus citations

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.

Original languageEnglish
Article number529
JournalScientific reports
Volume2
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

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    Ishigaki, S., Masuda, A., Fujioka, Y., Iguchi, Y., Katsuno, M., Shibata, A., Urano, F., Sobue, G., & Ohno, K. (2012). Position-dependent FUS-RNA interactions regulate alternative splicing events and transcriptions. Scientific reports, 2, [529]. https://doi.org/10.1038/srep00529