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Defining the contribution of microRNA-specific Argonautes with slicer capability in animals.

Anisha Pal | Vaishnav Vasudevan | François Houle | Michael Lantin | Katherine A Maniates | Miguel Quévillon Huberdeau | Allison L Abbott | Martin J Simard
Nucleic acids research | 2024

microRNAs regulate gene expression through interaction with an Argonaute protein. While some members of this protein family retain an enzymatic activity capable of cleaving RNA molecules complementary to Argonaute-bound small RNAs, the role of the slicer residues in the canonical microRNA pathway is still unclear in animals. To address this, we created Caenorhabditis elegans strains with mutated slicer residues in the endogenous ALG-1 and ALG-2, the only two slicing Argonautes essential for the miRNA pathway in this animal model. We observe that the mutation in ALG-1 and ALG-2 catalytic residues affects overall animal fitness and causes phenotypes reminiscent of miRNA defects only when grown and maintained at restrictive temperature. Furthermore, the analysis of global miRNA expression shows that the slicer residues of ALG-1 and ALG-2 contribute differentially to regulate the level of specific subsets of miRNAs in young adults. We also demonstrate that altering the catalytic tetrad of those miRNA-specific Argonautes does not result in any defect in the production of canonical miRNAs. Together, these data support that the slicer residues of miRNA-specific Argonautes contribute to maintaining levels of a set of miRNAs for optimal viability and fitness in animals particularly exposed to specific growing conditions.

Pubmed ID: 38477356

Antibodies used in this publication

None found

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: K12 GM093854
  • Agency: NIH HHS, United States
    Id: GM126458
  • Agency: NIGMS NIH HHS, United States
    Id: R15 GM126458
  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: CIHR, Canada
    Id: PJT-173445

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