Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging

Antti P Aalto, Ian A Nicastro, James P Broughton, Laura B Chipman, William P Schreiner, Jerry S Chen, Amy E Pasquinelli

Research output: Contribution to journalArticleScientificpeer-review

32 Citations (Scopus)


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.

Original languageEnglish
Article numbere1007379
JournalPLoS Genetics
Issue number6
Publication statusPublished - Jun 2018
MoE publication typeA1 Journal article-refereed


  • Animals
  • Argonaute Proteins/physiology
  • Caenorhabditis elegans/physiology
  • Caenorhabditis elegans Proteins/genetics
  • Forkhead Transcription Factors/physiology
  • Gene Expression Regulation, Developmental
  • Genes, Helminth
  • Insulin/metabolism
  • Insulin-Like Growth Factor I/metabolism
  • Longevity/genetics
  • MicroRNAs/physiology
  • Mutation
  • RNA, Helminth/physiology
  • RNA-Binding Proteins/physiology
  • Receptor, Insulin/genetics
  • Signal Transduction/physiology


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