PIWI-interacting RNA expression regulates pathogenesis in a Caenorhabditis elegans model of Lewy body disease.

ABSTRACT: PIWI-interacting RNAs (piRNAs) are small noncoding RNAs that regulate gene expression, yet their molecular functions in neurobiology are unclear. While investigating neurodegeneration mechanisms using human α-syn(A53T)^Tg and Aβ^Tg;α-syn(A53T)^Tg pan-neuronal overexpressing strains, we unexpectedly observed dysregulation of piRNAs. RNAi screening revealed that knock down of piRNA biogenesis genes improved thrashing behavior; further, a tofu-1 gene deletion ameliorated phenotypic deficits in α-syn(A53T)^Tg and Aβ^Tg;α-syn(A53T)^Tg transgenic strains. piRNA expression was extensively downregulated and H3K9me3 marks were decreased after tofu-1 deletion in α-syn(A53T)^Tg and Aβ^Tg;α-syn(A53T)^Tg strains.

SUBMITTER: Huang X 

PROVIDER: S-EPMC10545829 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature