| Full text | |
| Author(s): Show less - |
Camara, Henrique
;
Inan, Mehmet Dincer
;
Vergani Jr, Carlos A.
;
Pinto, Silas
;
Knittel, Thiago L.
;
Salgueiro, Willian G.
;
Tonon-da-Silva, Guilherme
;
Ramirez, Juliana
;
de Moraes, Diogo
;
Braga, Deisi L.
;
De-Souza, Evandro A.
;
Mori, Marcelo A.
Total Authors: 12
|
| Document type: | Journal article |
| Source: | Gene; v. 895, p. 11-pg., 2023-11-25. |
| Abstract | |
Intertissue RNA transport recently emerged as a novel signaling mechanism. In mammals, mounting evidence suggests that small RNA transfer between cells is widespread and used in various physiological contexts. In the nematode C. elegans, a similar mechanism is conferred by the systemic RNAi pathway. Members of the Systemic RNA Interference Defective (SID) family act at different steps of cellular RNA uptake and export. The limiting step in systemic RNA interference (RNAi) is the import of extracellular RNAs via the conserved double-stranded (dsRNA)-gated dsRNA channel SID-1. To better understand the role of RNAs as intertissue signaling molecules, we modified the function of SID-1 in specific tissues of C. elegans. We observed that sid-1 loss-of-function mutants are as healthy as wild-type worms. Conversely, overexpression of sid-1 in C. elegans intestine, muscle, or neurons rendered worms short-lived. The effects of intestinal sid-1 overexpression were attenuated by silencing the components of systemic RNAi sid-1, sid-2 and sid-5, implicating systemic RNA signaling in the lifespan reduction. Accordingly, tissue-specific overexpression of sid-2 and sid-5 also reduced worm lifespan. Additionally, an RNAi screen for components of several non-coding RNA pathways revealed that silencing the miRNA biogenesis proteins PASH-1 and DCR-1 rendered the lifespan of worms with intestinal sid-1 overexpression similar to controls. Collectively, our data support the notion that systemic RNA signaling must be tightly regulated, and unbalancing that process provokes a reduction in lifespan. We termed this phenomenon Intercellular/Extracellular Systemic RNA imbalance (InExS). (AU) | |
| FAPESP's process: | 17/01339-2 - Uncovering mechanisms of longevity mediated by mobile RNAs |
| Grantee: | Henrique Camara |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 19/25958-9 - DecAI: decoding aging initiative |
| Grantee: | Marcelo Alves da Silva Mori |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 21/08354-2 - The interplay between the immune system and metabolism as a key determinant of the aging process |
| Grantee: | Marcelo Alves da Silva Mori |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/01184-9 - CAMeLEOm: cross-species analysis of metabolic, lifespan effects and omics of dietary restriction mimetics |
| Grantee: | Marcelo Alves da Silva Mori |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 15/04264-8 - Phenotypic screen of nematodes C. elegans mutants for proteins necessary to systemic RNAi |
| Grantee: | Henrique Camara |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 19/01587-1 - Study of the role of ALG-1 and its regulatory mechanisms in healthspan of Caenorhabditis elegans |
| Grantee: | Carlos Alberto Vergani Junior |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 14/10814-8 - Determination of factors that controls Dicer expression in vivo in C. elegans |
| Grantee: | Evandro Araújo de Souza |
| Support Opportunities: | Scholarships in Brazil - Master |