Mutations in Conserved Residues of the microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression

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microRNAs are small non-coding RNAs that function in diverse processes by post-transcriptionally regulating gene expression. Argonautes form the core of the microRNA Induced Silencing Complex (miRISC) and are required for microRNA biogenesis and function. Here we describe the identification and characterization of a novel set of mutations in alg-1, a Caenorhabditis elegans microRNA specific Argonaute. This new class of alg-1 mutations causes phenotypes more severe than the complete loss of alg-1. Interestingly, the mutant ALG-1 proteins are able to promote microRNA biogenesis, but are defective in mediating microRNA target gene repression. We found that mutant ALG-1 associates more with Dicer, but less with miRISC effector AIN-1, compared to wild type ALG-1. We propose that these mutant ALG-1 proteins assemble nonfunctional complexes that effectively compete with the paralogous ALG-2 for critical miRISC components, including mature microRNAs. This new class of Argonaute mutants highlights the role of Argonaute in mediating a functional transition for miRISC from microRNA processing phase to target repression phase.

Vyšlo v časopise: Mutations in Conserved Residues of the microRNA Argonaute ALG-1 Identify Separable Functions in ALG-1 miRISC Loading and Target Repression. PLoS Genet 10(4): e32767. doi:10.1371/journal.pgen.1004286
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004286

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