Shah, Vivek Nilesh and Neumeier, Julia and Huberdeau, Miguel Quevillon and Zeitler, Daniela M. and Bruckmann, Astrid and Meister, Gunter and Simard, Martin J. (2023) Casein kinase 1 and 2 phosphorylate Argonaute proteins to regulate miRNA-mediated gene silencing. EMBO REPORTS, 24 (11). ISSN 1469-221X, 1469-3178
Full text not available from this repository. (Request a copy)Abstract
MicroRNAs (miRNAs) together with Argonaute (AGO) proteins form the core of the RNA-induced silencing complex (RISC) to regulate gene expression of their target RNAs post-transcriptionally. Argonaute proteins are subjected to intensive regulation via various post-translational modifications that can affect their stability, silencing efficacy and specificity for targeted gene regulation. We report here that in Caenorhabditis elegans, two conserved serine/threonine kinases - casein kinase 1 alpha 1 (CK1A1) and casein kinase 2 (CK2) - regulate a highly conserved phosphorylation cluster of 4 Serine residues (S988:S998) on the miRNA-specific AGO protein ALG-1. We show that CK1A1 phosphorylates ALG-1 at sites S992 and S995, while CK2 phosphorylates ALG-1 at sites S988 and S998. Furthermore, we demonstrate that phospho-mimicking mutants of the entire S988:S998 cluster rescue the various developmental defects observed upon depleting CK1A1 and CK2. In humans, we show that CK1A1 also acts as a priming kinase of this cluster on AGO2. Altogether, our data suggest that phosphorylation of AGO within the cluster by CK1A1 and CK2 is required for efficient miRISC-target RNA binding and silencing.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSLATIONAL REPRESSION; CAENORHABDITIS-ELEGANS; SUBSTRATE-SPECIFICITY; RNA; INTERFERENCE; SEQUENCE; NEMATODE; CLEAVAGE; TARGET; CK2; Argonaute; CK2; microRNA; phosphorylation |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Mar 2024 13:37 |
| Last Modified: | 13 Mar 2024 13:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59957 |
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