Reference - Detail
| RRC ID | 80890 |
|---|---|
| Author | Huang X, Wang C, Zhang T, Li R, Chen L, Leung KL, Lakso M, Zhou Q, Zhang H, Wong G. |
| Title | PIWI-interacting RNA expression regulates pathogenesis in a Caenorhabditis elegans model of Lewy body disease. |
| Journal | Nat Commun |
| 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 AβTg;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 AβTg;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 AβTg;α-syn(A53T)Tg strains. Dysregulated piRNAs targeted protein degradation genes suggesting that a decrease of piRNA expression leads to an increase of degradation ability in C. elegans. Finally, we interrogated piRNA expression in brain samples from PD patients. piRNAs were observed to be widely overexpressed at late motor stage. In this work, our results provide evidence that piRNAs are mediators in pathogenesis of Lewy body diseases and suggest a molecular mechanism for neurodegeneration in these and related disorders. |
| Volume | 14(1) |
| Pages | 6137 |
| Published | 2023-10-2 |
| DOI | 10.1038/s41467-023-41881-8 |
| PII | 10.1038/s41467-023-41881-8 |
| PMID | 37783675 |
| PMC | PMC10545829 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Humans Lewy Body Disease* / genetics Piwi-Interacting RNA RNA, Small Interfering / metabolism |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| C.elegans | tm872 tm6424 tm1978 |