FUS‐mediated regulation of alternative RNA processing in neurons: insights from global transcriptome analysis. (28th January 2016)

• Record Type: Journal Article
• Authors: Masuda, Akio; Takeda, Jun‐ichi; Ohno, Kinji
• Is Part Of: Wiley interdisciplinary reviews. Volume 7:Number 3(2016:May/Jun.)
• Page Start: 330
• Page End: 340
• Publication Date: 2016-01-28
• Subjects: RNA -- Periodicals; 572.8805
• DOI: 10.1002/wrna.1338
• Languages: English
• ISSNs: 1757-7004

Abstract

Abstract : Fused in sarcoma (FUS) is an RNA‐binding protein that is causally associated with oncogenesis and neurodegeneration. Recently, the role of FUS in neurodegeneration has been extensively studied, because mutations in FUS are associated with amyotrophic lateral sclerosis (ALS), and the FUS protein has been identified as a major component of intracellular inclusions in neurodegenerative disorders including ALS and frontotemporal lobar degeneration. FUS is a key molecule in transcriptional regulation and RNA processing including processes such as pre‐messenger RNA (mRNA) splicing and polyadenylation. Interaction of FUS with various components of the transcription machinery, spliceosome, and the 3′‐end processing machinery has been identified. Furthermore, recent advances in high‐throughput transcriptomic profiling approaches have enabled us to determine the mechanisms of FUS‐dependent RNA processing networks at a cellular level. These analyses have revealed that depletion of FUS in neuronal cells affects alternative splicing and alternative polyadenylation of thousands of mRNAs. Gene ontology analysis has suggested that FUS‐modulated genes are implicated in neuronal functions and development. CLIP‐seq of FUS has shown that FUS is frequently clustered around these alternative sites of nascent RNA. ChIP‐seq of RNA polymerase II (RNAP II) has demonstrated that an interaction between FUS and nascent RNA downregulates local transcriptional activity of RNAP II, which is critically involved in RNA processing. Both alternative splicing and alternative polyadenylation are fundamental processes by which cells expand their transcriptomic diversity, and are particularly essential in the nervous system. Dependence of transcriptomic diversity on FUS makes the nervous system vulnerable to neurodegeneration, when FUS is functionally compromised. WIREs RNA 2016, 7:330–340. doi: 10.1002/wrna.1338 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications RNA Processing > Splicing Regulation/Alternative Splicing RNA Processing > 3' End Processing