ALG-5 is a miRNA-associated Argonaute required for proper developmental timing in the Caenorhabditis elegans germline

Nucleic Acids Res. 2017 Sep 6;45(15):9093-9107. doi: 10.1093/nar/gkx536.


Caenorhabditis elegans contains 25 Argonautes, of which, ALG-1 and ALG-2 are known to primarily interact with miRNAs. ALG-5 belongs to the AGO subfamily of Argonautes that includes ALG-1 and ALG-2, but its role in small RNA pathways is unknown. We analyzed by high-throughput sequencing the small RNAs associated with ALG-5, ALG-1 and ALG-2, as well as changes in mRNA expression in alg-5, alg-1 and alg-2 mutants. We show that ALG-5 defines a distinct branch of the miRNA pathway affecting the expression of genes involved in immunity, defense, and development. In contrast to ALG-1 and ALG-2, which associate with most miRNAs and have general roles throughout development, ALG-5 interacts with only a small subset of miRNAs and is specifically expressed in the germline where it localizes alongside the piRNA and siRNA machinery at P granules. alg-5 is required for optimal fertility and mutations in alg-5 lead to a precocious transition from spermatogenesis to oogenesis. Our results provide a near-comprehensive analysis of miRNA-Argonaute interactions in C. elegans and reveal a new role for miRNAs in the germline.

MeSH terms

  • Animals
  • Argonaute Proteins / genetics*
  • Argonaute Proteins / metabolism
  • Caenorhabditis elegans / classification
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Gene Expression Regulation, Developmental*
  • Germ Cells / growth & development
  • Germ Cells / metabolism*
  • Hermaphroditic Organisms / genetics
  • Hermaphroditic Organisms / growth & development
  • Hermaphroditic Organisms / metabolism
  • High-Throughput Nucleotide Sequencing
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mutation
  • Oogenesis / genetics
  • Phylogeny
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Helminth / genetics*
  • RNA, Helminth / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Spermatogenesis / genetics


  • ALG-1 protein, C elegans
  • ALG-2 protein, C elegans
  • ALG-5 protein, C elegans
  • Argonaute Proteins
  • Caenorhabditis elegans Proteins
  • MicroRNAs
  • Protein Isoforms
  • RNA, Helminth
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins