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Small RNA-mediated genetic switches coordinate ALG-3/4 small RNA pathway function.

Trilotma Sen | Cara McCormick | Alicia K Rogers
Nucleic acids research | 2024

Coordination of gene regulatory networks is necessary for proper execution of cellular programs throughout development. RNA interference (RNAi) is an essential regulatory mechanism in all metazoans. Proper RNAi-mediated gene regulation requires coordination of several RNAi branches to ensure homeostasis. For example, in Caenorhabditis elegans, the Argonautes, ALG-3 and ALG-4, are expressed specifically during spermatogenesis (L4 stage) and bind small interfering RNAs (siRNAs) complementary to sperm-enriched genes. We find that alg-3 and alg-4 are regulated by siRNAs. Our work shows that gene switches are operated via these siRNAs to regulate the Argonautes' expression in a temporal manner. This RNAi-to-RNAi regulatory cascade is essential for coordinating ALG-3/4 pathway function, particularly during heat stress, to provide thermotolerant sperm-based fertility. This work provides insight into one regulatory motif used to maintain RNAi homeostasis, across developmental stages, despite environmental stressors. As RNAi pathways are evolutionarily conserved, other species likely use similar regulatory architectures to maintain RNAi homeostasis.

Pubmed ID: 38967024

Antibodies used in this publication

None found

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NCI NIH HHS, United States
    Id: P30 CA014089
  • Agency: University of Texas at Arlington,
  • Agency: American Cancer Society Postdoctoral Fellowship,
    Id: PF-20-129-01-DDC
  • Agency: University of Texas System Rising STARs,

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