title: The ALS/FTLD-related RNA-binding proteins TDP-43 and FUS have common downstream RNA targets in cortical neurons.
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.
authors: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Daiyu
authors: D
authors: Honda
authors: Shinsuke
authors: S
authors: Ishigaki
authors: Yohei
authors: Y
authors: Iguchi
authors: Yusuke
authors: Y
authors: Fujioka
authors: Tsuyoshi
authors: T
authors: Udagawa
authors: Akio
authors: A
authors: Masuda
authors: Kinji
authors: K
authors: Ohno
authors: Masahisa
authors: M
authors: Katsuno
authors: Gen
authors: G
authors: Sobue
keywords: ALS; ALS, amyotrophic lateral sclerosis; Cugbp1, CUG triplet  repeat, RNA-binding protein 1; DAVID, Database for  Annotation, Visualization and Integrated Discovery; FTLD; FTLD, frontotemporal lobar degeneration; FUS; FUS, fused in sarcoma; GFAP, glial fibrillary acidic protein; GO, Gene Ontology; LTP, long-term potentiation; RIN, RNA integrity numbers; RMA, robust multichip average; RRMs, RNA recognition motifs; SBMA, spinal and bulbar muscular atrophy; TDP-43; TDP-43, transactive response (TAR) DNA-binding protein 43; TGF, transforming growth factor; Transcriptome; hnRNAPs, heterogeneous ribonucleoproteins; shCont, shRNA/control; shCugbp1, shRNA/Cugbp1; shFUS, shRNA/FUS; shTDP, shRNA/TDP-43