%0 Journal Article
%T Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging
%A Amy E. Pasquinelli
%A Antti P. Aalto
%A Ian A. Nicastro
%A James P. Broughton
%A Jerry S. Chen
%A Laura B. Chipman
%A William P. Schreiner
%J -
%D 2018
%R 10.1371/journal.pgen.1007379
%X 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
%K MicroRNAs
%K RNA interference
%K Caenorhabditis elegans
%K Gene expression
%K 3' UTR
%K Phenotypes
%K RNA sequencing
%K Gene regulation
%U https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007379