Disappearance of TAR-DNA-binding protein 43 kDa (TDP-43) from the nucleus 
contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS), but the 
nuclear function of TDP-43 is not yet fully understood. TDP-43 associates with 
nuclear bodies including Gemini of coiled bodies (GEMs). GEMs contribute to the 
biogenesis of uridine-rich small nuclear RNA (U snRNA), a component of splicing 
machinery. The number of GEMs and a subset of U snRNAs decrease in spinal 
muscular atrophy, a lower motor neuron disease, suggesting that alteration of U 
snRNAs may also underlie the molecular pathogenesis of ALS. Here, we 
investigated the number of GEMs and U11/12-type small nuclear ribonucleoproteins 
(snRNP) by immunohistochemistry and the level of U snRNAs using real-time 
quantitative RT-PCR in ALS tissues. GEMs decreased in both TDP-43-depleted HeLa 
cells and spinal motor neurons in ALS patients. Levels of several U snRNAs 
decreased in TDP-43-depleted SH-SY5Y and U87-MG cells. The level of U12 snRNA 
was decreased in tissues affected by ALS (spinal cord, motor cortex and 
thalamus) but not in tissues unaffected by ALS (cerebellum, kidney and muscle). 
Immunohistochemical analysis revealed the decrease in U11/12-type snRNP in 
spinal motor neurons of ALS patients. These findings suggest that loss of TDP-43 
function decreases the number of GEMs, which is followed by a disturbance of 
pre-mRNA splicing by the U11/U12 spliceosome in tissues affected by ALS.