Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging.

Autor: Antti P Aalto, Ian A Nicastro, James P Broughton, Laura B Chipman, William P Schreiner, Jerry S Chen, Amy E Pasquinelli
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS Genetics, Vol 14, Iss 6, p e1007379 (2018)
Druh dokumentu: article
ISSN: 1553-7390
1553-7404
DOI: 10.1371/journal.pgen.1007379
Popis: Argonaute (AGO) proteins partner with microRNAs (miRNAs) to target specific genes for post-transcriptional regulation. During larval development in Caenorhabditis elegans, Argonaute-Like Gene 1 (ALG-1) is the primary mediator of the miRNA pathway, while the related ALG-2 protein is largely dispensable. Here we show that in adult C. elegans these AGOs are differentially expressed and, surprisingly, work in opposition to each other; alg-1 promotes longevity, whereas alg-2 restricts lifespan. Transcriptional profiling of adult animals revealed that distinct miRNAs and largely non-overlapping sets of protein-coding genes are misregulated in alg-1 and alg-2 mutants. Interestingly, many of the differentially expressed genes are downstream targets of the Insulin/ IGF-1 Signaling (IIS) pathway, which controls lifespan by regulating the activity of the DAF-16/ FOXO transcription factor. Consistent with this observation, we show that daf-16 is required for the extended lifespan of alg-2 mutants. Furthermore, the long lifespan of daf-2 insulin receptor mutants, which depends on daf-16, is strongly reduced in animals lacking alg-1 activity. This work establishes an important role for AGO-mediated gene regulation in aging C. elegans and illustrates that the activity of homologous genes can switch from complementary to antagonistic, depending on the life stage.
Databáze: Directory of Open Access Journals
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