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| Status |
Public on Sep 12, 2023 |
| Title |
Casein kinase 1 and 2 phosphorylate Argonaute proteins to regulate miRNA-mediated gene silencing |
| Organism |
Caenorhabditis elegans |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
To evaluate the effects on global miRNA levels after CK1A1 and CK2 depletion in wild-type animals by HT-sequencing
The control RNAi is control treatment. And the kin-19 RNAi corresponds to CK1A1 depletion. CK1A1 is the ortholog of kin-19 in C elegans. And, kin-3 RNAi and kin-10 RNAi correspond to CK2 depletion. As CK2 is made of two subunits, kin-3 (catalytic) and kin-10 (regulatory) in C. elegans.
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| Web link |
https://www.embopress.org/doi/abs/10.15252/embr.202357250
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| Contributor(s) |
Shah VN, Neumeier J, Quévillon Huberdeau M, Zeitler DM, Bruckmann A, Meister G, Simard MJ |
| Citation(s) |
37712432 |
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| Submission date |
Jul 27, 2023 |
| Last update date |
Dec 13, 2023 |
| Contact name |
VIVEK NILESH SHAH |
| E-mail(s) |
Vivek.Shah@crchudequebec.ulaval.ca
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| Phone |
4185208754
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| Organization name |
Université Laval
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| Department |
Département de biologie moléculaire, de biochimie médicale et de pathologie
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| Lab |
Dr. Martin Simard
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| Street address |
9 Rue McMahon
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| City |
Québec |
| State/province |
Québec |
| ZIP/Postal code |
G1R3S3 |
| Country |
Canada |
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| Platforms (1) |
| GPL22765 |
Illumina HiSeq 4000 (Caenorhabditis elegans) |
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| Samples (16)
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| GSM7665333 |
N2, kin-10 RNAi, rep 1 |
| GSM7665334 |
N2, control RNAi, rep 2 |
| GSM7665335 |
N2, kin-19 RNAi, rep 2 |
| GSM7665336 |
N2, kin-3 RNAi, rep 2 |
| GSM7665337 |
N2, kin-10 RNAi, rep 2 |
| GSM7665338 |
N2, control RNAi, rep 3 |
| GSM7665339 |
N2, kin-19 RNAi, rep 3 |
| GSM7665340 |
N2, kin-3 RNAi, rep 3 |
| GSM7665341 |
N2, kin-10 RNAi, rep 3 |
| GSM7665342 |
N2, control RNAi, rep 4 |
| GSM7665343 |
N2, kin-19 RNAi, rep 4 |
| GSM7665344 |
N2, kin-3 RNAi, rep 4 |
| GSM7665345 |
N2, kin-10 RNAi, rep 4 |
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| Relations |
| BioProject |
PRJNA999321 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE239453_RAW.tar |
30.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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