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

A specific type of Argonaute phosphorylation regulates binding to microRNAs during C. elegans development.
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DOI:
10.1016/j.celrep.2022.111822
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发表时间:
2022-12-13
期刊:
影响因子:
8.8
通讯作者:
--
中科院分区:
生物学1区
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--
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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 reveal 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 the protein kinase A (PKA) KIN-1 as the putative kinase that phosphorylates ALG-1 serine 642. Altogether, our data indicate that PKA triggers the ALG-1 phosphorylation to regulate its microRNAs association during C. elegans development.
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