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Publication : A specific type of Argonaute phosphorylation regulates binding to microRNAs during C. elegans development.

First Author  Quévillon Huberdeau M Year  2022
Journal  Cell Rep Volume  41
Issue  11 Pages  111822
PubMed ID  36516777 Mgi Jnum  J:352585
Mgi Id  MGI:7707640 Doi  10.1016/j.celrep.2022.111822
Citation  Quevillon Huberdeau M, et al. (2022) A specific type of Argonaute phosphorylation regulates binding to microRNAs during C. elegans development. Cell Rep 41(11):111822
abstractText  Argonaute proteins are at the core of the microRNA-mediated gene silencing pathway essential for animals. In C. elegans, the microRNA-specific Argonautes ALG-1 and ALG-2 regulate multiple processes required for proper animal developmental timing and viability. Here we identified a phosphorylation site on ALG-1 that modulates microRNA association. Mutating ALG-1 serine 642 into a phospho-mimicking residue impairs microRNA binding and causes embryonic lethality and post-embryonic phenotypes that are consistent with alteration of microRNA functions. Monitoring microRNA levels in alg-1 phosphorylation mutant animals shows that microRNA passenger strands increase in abundance but are not preferentially loaded into ALG-1, indicating that the miRNA binding defects could lead to microRNA duplex accumulation. Our genetic and biochemical experiments support protein kinase A (PKA) KIN-1 as the putative kinase that phosphorylates ALG-1 serine 642. Our data indicate that PKA triggers ALG-1 phosphorylation to regulate its microRNA association during C. elegans development.
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