GSE120335
Defective expression of mitochondrial, histone and vesicle genes in a C. elegans SMA model
Spinal muscular atrophy (SMA) is a severe congenital motor neuron degenerative disease caused by loss-of-function mutations in the conserved survival motor neuron gene SMN1. SMN is required for the assembly of small nuclear ribonucleoprotein complexes, the core components of the spliceosome and also affects other molecular processes. It is hypothesized that defective gene expression and pre-mRNA splicing underlie SMA. However the immediate target genes of SMN are unclear. We used the nematode Caenorhabditis elegans as a model to study the function of SMN. We analyzed the transcriptome of a C. elegans smn-1 deletion mutant and identified that multiple biological processes were affected. Specifically the expression of numerous mitochondrial genes and vacuolar H+ -ATPase was significantly reduced while the expression of multiple histone genes was significantly increased. We also found that the U2AF large subunit mutation n4588 could ameliorate the defective expression of genes in the mitochondrial and V-ATPase pathways caused by the smn-1 mutation, which is consistent with our previous finding that uaf-1(n4588) could improve the behavior and lifespan of smn-1 mutants. Our study identified key molecular processes affected by SMN and suggests that mitochondrial and V-ATPase dysfunctions might contribute to SMA. Overall design: Detect expression differences across N2, smn-1(ok355), uaf-1(n4588) and smn-1(ok355); uaf-1(n4588) on day 2 post the L1 larval stage. At least two replicates were used for each genotype.