FUS-regulated region- and cell-type-specific transcriptome is associated with cell selectivity in ALS/FTLD.
FUS is genetically and pathologically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). To clarify the RNA metabolism cascade regulated by FUS in ALS/FTLD, we compared the FUS-regulated transcriptome profiles in different lineages of primary cells from the central nervous system. The profiles of FUS-mediated gene expression and alternative splicing in motor neurons were similar to those of cortical neurons, but not to those in cerebellar neurons despite the similarity of innate transcriptome signature. The gene expression profiles in glial cells were similar to those in motor and cortical neurons. We identified certain neurological diseases-associated genes, including Mapt, Stx1a, and Scn8a, among the profiles of gene expression and alternative splicing events regulated by FUS. Thus, FUS-regulated transcriptome profiles in each cell-type may determine cellular fate in association with FUS-mediated ALS/FTLD, and identified RNA targets for FUS could be therapeutic targets for ALS/FTLD.
Department of Neurology, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yusuke
Y
Fujioka
Shinsuke
S
Ishigaki
Akio
A
Masuda
Yohei
Y
Iguchi
Tsuyoshi
T
Udagawa
Hirohisa
H
Watanabe
Masahisa
M
Katsuno
Kinji
K
Ohno
Gen
G
Sobue
D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D014018:Tissue Distribution; D059467:Transcriptome
D009419:Nerve Tissue Proteins; D034702:RNA-Binding Protein FUS