{"doi":"10.1101/2022.11.23.517635","title":"Tissue-specific overexpression of the double-stranded RNA transporter SID-1 limits lifespan in <i>C. elegans</i>","abstract":"ABSTRACT Intertissue RNA transport has emerged as a novel signaling mechanism. In C. elegans , this is conferred by the systemic RNAi pathway, in which the limiting step is the cellular import of extracellular RNAs via SID-1. To better understand the physiological role of systemic RNAi in vivo , we modified the function of SID-1 through loss-of-function mutation and tissue-specific overexpression of sid-1 in C. elegans . We observed that sid-1 loss-of-function mutants are as healthy as wild-type worms. Conversely, overexpression of sid-1 in intestine, muscle, or neurons rendered worms short-lived. The effects of intestinal sid-1 overexpression were reversed by silencing the components of the systemic RNAi pathway sid-1, sid-2 and sid-5 , thus implicating RNA transport. Moreover, silencing the miRNA biogenesis proteins pash-1 and dcr-1 rendered the lifespan of worms with intestinal sid-1 overexpression similar to controls. Lastly, we observed that the lifespan decrease produced by tissue-specific sid-1 overexpression was dependent on the bacterial food source. Collectively, our data support the notion that systemic RNA signaling is tightly regulated, and unbalancing that process provokes a reduction in lifespan.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313291,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1012001,"name":"Carlos A. Vergani-Junior","orcid":null,"position":1,"is_corresponding":false},{"id":463051,"name":"Silas Pinto","orcid":"0000-0003-0894-8915","position":2,"is_corresponding":false},{"id":463056,"name":"Thiago L. Knittel","orcid":"0000-0001-5716-2033","position":3,"is_corresponding":false},{"id":1012002,"name":"Willian G. Salgueiro","orcid":null,"position":4,"is_corresponding":false},{"id":1011544,"name":"Guilherme Tonon-da-Silva","orcid":"0000-0003-3222-9654","position":5,"is_corresponding":false},{"id":1012003,"name":"Juliana Ramirez","orcid":null,"position":6,"is_corresponding":false},{"id":525300,"name":"Evandro A. De‐Souza","orcid":"0000-0002-9080-3864","position":7,"is_corresponding":false},{"id":463062,"name":"Marcelo A. Mori","orcid":"0000-0001-7112-5263","position":8,"is_corresponding":false},{"id":525301,"name":"Henrique Camara","orcid":"0000-0001-7300-1416","position":0,"is_corresponding":true}],"reference_count":32,"raw_metadata":null,"created_at":"2026-07-19T00:33:44.454239Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}