PXD043913-1

PXD043913 is an original dataset announced via ProteomeXchange.

Title	Casein kinase 1 and 2 phosphorylate a conserved cluster of Argonaute to control microRNA functionCasein kinase 1 and 2 phosphorylate a conserved cluster of Argonaute to control microRNA function
Description	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 C. 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
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_03:58:18.264.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD043913
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Astrid Bruckmann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidoethyl-L-cysteine; phosphorylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-19 06:11:12	ID requested
⏵ 1	2024-10-17 03:58:19	announced

Shah VN, Neumeier J, Huberdeau MQ, Zeitler DM, Bruckmann A, Meister G, Simard MJ, Casein kinase 1 and 2 phosphorylate Argonaute proteins to regulate miRNA-mediated gene silencing. EMBO Rep, 24(11):e57250(2023) [pubmed]

10.6019/PXD043913;

10.15252/embr.202357250;

submitter keyword: Argonaute/CK1A1/CK2/microRNA/phosphorylation

Astrid Bruckmann
contact affiliation	University Regensburg Biochemistry I Mass Spectrometry group
contact email	astrid.bruckmann@ur.de
lab head
Astrid Bruckmann
contact affiliation	University Regensburg
contact email	astrid.bruckmann@ur.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043913
     1. Label: PRIDE project
     2. Name: Casein kinase 1 and 2 phosphorylate a conserved cluster of Argonaute to control microRNA functionCasein kinase 1 and 2 phosphorylate a conserved cluster of Argonaute to control microRNA function