Protein aggregate/inclusion is one of hallmarks for neurodegenerative disorders 
including amyotrophic lateral sclerosis (ALS). FUS/TLS, one of causative genes 
for familial ALS, encodes a multifunctional DNA/RNA binding protein 
predominantly localized in the nucleus. C-terminal mutations in FUS/TLS cause 
the retention and the inclusion of FUS/TLS mutants in the cytoplasm. In the 
present study, we examined the effects of ALS-linked FUS mutants on 
ALS-associated RNA binding proteins and RNA granules. FUS C-terminal mutants 
were diffusely mislocalized in the cytoplasm as small granules in transiently 
transfected SH-SY5Y cells, whereas large aggregates were spontaneously formed in 
∼10% of those cells. hnRNP A1, hnRNP A2, and SMN1 as well as FUS wild type were 
assembled into stress granules under stress conditions, and these were also 
recruited to FUS mutant-derived spontaneous aggregates in the cytoplasm. These 
aggregates stalled poly(A) mRNAs and sequestered SMN1 in the detergent insoluble 
fraction, which also reduced the number of nuclear oligo(dT)-positive foci 
(speckles) in FISH (fluorescence in situ hybridization) assay. In addition, the 
number of P-bodies was decreased in cells harboring cytoplasmic granules of FUS 
P525L. These findings raise the possibility that ALS-linked C-terminal FUS 
mutants could sequester a variety of RNA binding proteins and mRNAs in the 
cytoplasmic aggregates, which could disrupt various aspects of RNA equilibrium 
and biogenesis.