The ALS/FTLD‐related RNA‐binding proteins TDP‐43 and FUS have common downstream RNA targets in cortical neurons. Issue 1 (20th November 2013)

• Record Type: Journal Article
• Authors: Honda, Daiyu; Ishigaki, Shinsuke; Iguchi, Yohei; Fujioka, Yusuke; Udagawa, Tsuyoshi; Masuda, Akio; Ohno, Kinji; Katsuno, Masahisa; Sobue, Gen
• Is Part Of: FEBS open bio. Volume 4:Issue 1(2014)
• Page Start: 1
• Page End: 10
• Publication Date: 2013-11-20
• Subjects: ALS -- FTLD -- TDP-43 -- FUS -- Transcriptome; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.fob.2013.11.001
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : TDP‐43 and FUS are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), and loss of function of either protein contributes to these neurodegenerative conditions. To elucidate the TDP‐43‐ and FUS‐regulated pathophysiological RNA metabolism cascades, we assessed the differential gene expression and alternative splicing profiles related to regulation by either TDP‐43 or FUS in primary cortical neurons. These profiles overlapped by >25% with respect to gene expression and >9% with respect to alternative splicing. The shared downstream RNA targets of TDP‐43 and FUS may form a common pathway in the neurodegenerative processes of ALS/FTLD. Abstract : We established TDP‐43‐silenced primary cortical neurons using lentivirus. We compared TDP‐43 and FUS transcriptome profiles in primary cortical neurons. The sets of genes with altered expression levels upon TDP‐43 knockdown or FUS knockdown overlapped by >25%. The sets of genes with altered exon splicing upon TDP‐43 knockdown or FUS knockdown overlapped by >9%.