Huberdeau, Miguel Quevillon and Zeitler, Daniela M. and Hauptmann, Judith and Bruckmann, Astrid and Fressigne, Lucile and Danner, Johannes and Piquet, Sandra and Strieder, Nicholas and Engelmann, Julia C. and Jannot, Guillaume and Deutzmann, Rainer and Simard, Martin J. and Meister, Gunter (2017) Phosphorylation of Argonaute proteins affects mRNA binding and is essential for microRNA-guided gene silencing in vivo. EMBO JOURNAL, 36 (14). pp. 2088-2106. ISSN 0261-4189, 1460-2075
Full text not available from this repository. (Request a copy)Abstract
Argonaute proteins associate with microRNAs and are key components of gene silencing pathways. With such a pivotal role, these proteins represent ideal targets for regulatory post-translational modifications. Using quantitative mass spectrometry, we find that a C-terminal serine/threonine cluster is phosphorylated at five different residues in human and Caenorhabditis elegans. In human, hyper-phosphorylation does not affect microRNA binding, localization, or cleavage activity of Ago2. However, mRNA binding is strongly affected. Strikingly, on Ago2 mutants that cannot bind microRNAs or mRNAs, the cluster remains unphosphorylated indicating a role at late stages of gene silencing. In C. elegans, the phosphorylation of the conserved cluster of ALG-1 is essential for microRNA function in vivo. Furthermore, a single point mutation within the cluster is sufficient to phenocopy the loss of its complete phosphorylation. Interestingly, this mutant retains its capacity to produce and bind microRNAs and represses expression when artificially tethered to an mRNA. Altogether, our data suggest that the phosphorylation state of the serine/threonine cluster is important for Argonaute-mRNA interactions.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CAENORHABDITIS-ELEGANS; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; PAZ DOMAIN; C-ELEGANS; MACROPHAGE ACTIVATION; SLICER ACTIVITY; RISC; COMPLEX; INTERFERENCE; Argonaute proteins; gene silencing; microRNA; phosphorylation; RISC |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 660 Chemical engineering |
| 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: | 14 Dec 2018 13:16 |
| Last Modified: | 13 Feb 2019 12:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1542 |
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