C. elegans PPM-2 regulates small RNA function by stabilizing Argonaute proteins
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ABSTRACT:
PROVIDER: PRJNA562557 | ENA |
REPOSITORIES: ENA
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Project description:Argonaute proteins associate with small non-coding RNAs such as microRNAs, piRNAs and siRNAs to regulate gene expression required for cell proliferation and differentiation. Thse Argonaute proteins are the major components of effector complexes of non-coding RNA pathways. In C. elegans, we identified PPM-2, a Mg2+/Mn2+-dependent serine/threonine phosphatase, as a new regulator of the small RNA pathways in C. elegans. We demonstrate that PPM-2 is involved in the regulation of the let-7 microRNA family but also in the regulation of nuclear RNAi as well as it contributes to the expression of piRNAs. The loss of ppm-2 affects the expression level of Type 1 piRNAs and the stability of ALG-1, PRG-1 and NRDE-3 Argonaute proteins by sending them to the proteasomal degradation pathway. Altogether, our findings suggest that PPM-2 is regulating the function of small non-coding RNA pathways by preventing Argonaute proteins to be degraded via the proteasomal pathway.
2021-08-01 | GSE136462 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE39746: Argonaute proteins couple chromatin silencing to alternative splicing (exon array) GSE39748: Argonaute proteins couple chromatin silencing to alternative splicing (RNA IP-Seq) Refer to individual Series
2012-08-22 | E-GEOD-39749 | biostudies-arrayexpress
Project description:Argonaute (AGO) proteins associate with small RNAs to direct their effector function on complementary transcripts. The nematode C. elegans contains an expanded family of 19 functional AGO proteins, many of which have not been fully characterized. In this work we systematically analyzed every C. elegans AGO, using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG tags. We have characterized the expression patterns of each AGO throughout development, identified small RNA binding complements, and determined the effects of ago loss on small RNA populations and developmental phenotypes. Our analysis indicates stratification of subsets of AGOs into distinct regulatory modules, and integration of our data led us to uncover novel stress-induced fertility and pathogen response phenotypes due to ago loss.
2022-07-22 | GSE208700 | GEO
Project description:Argonaute (AGO) proteins associate with small RNAs to direct their effector function on complementary transcripts. The nematode C. elegans contains an expanded family of 19 functional AGO proteins, many of which have not been fully characterized. In this work we systematically analyzed every C. elegans AGO, using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG tags. We have characterized the expression patterns of each AGO throughout development, identified small RNA binding complements, and determined the effects of ago loss on small RNA populations and developmental phenotypes. Our analysis indicates stratification of subsets of AGOs into distinct regulatory modules, and integration of our data led us to uncover novel stress-induced fertility and pathogen response phenotypes due to ago loss.
2022-07-22 | GSE208701 | GEO
Project 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
2023-09-13 | PXD044139 | Pride
Project 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 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.
2023-09-12 | GSE239453 | GEO
Project description:Small RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute proteins are produced as pro-proteins that are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a change of identity of 22G RNAs bound to these WAGO proteins. Accumulation of repeat- and transposon-derived transcripts, DNA damage and sterility ensue. We propose that DPF-3 acts as a licensing factor for 22G RNA activity.
2021-04-15 | GSE151716 | GEO
Project description:Small RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute proteins are produced as pro-proteins that are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a change of identity of 22G RNAs bound to these WAGO proteins. Accumulation of repeat- and transposon-derived transcripts, DNA damage and sterility ensue. We propose that DPF-3 acts as a licensing factor for 22G RNA activity.
2021-04-15 | GSE151715 | GEO
Project description:Small RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute proteins are produced as pro-proteins that are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a change of identity of 22G RNAs bound to these WAGO proteins. Accumulation of repeat- and transposon-derived transcripts, DNA damage and sterility ensue. We propose that DPF-3 acts as a licensing factor for 22G RNA activity.
2021-04-15 | GSE151714 | GEO
Project description:MicroRNAs are critical regulators of gene expression in animals. To repress their target mRNAs, these small RNAs are first loaded onto Argonaute proteins to form the silencing complex called miRISC. The complex must then be transported to its target mRNA where it interacts mostly within the 3’UTR through base-pairing. After target repression, the constituents of the miRISC undergo degradation or recycling mediated through their accurate sorting and localization in the cell. While some reports have linked intracellular trafficking to miRNA activity, it is still unclear how these pathways coordinate to allow proper miRNA-mediated gene silencing and turnover. Through a forward genetic screen performed in the nematode Caenorhabditis elegans, we identified the RabGAP tbc-11 as an important factor for the miRNA pathway. We show that TBC-11 is likely a GAP for the small GTPase RAB-6 and that its regulation is required for miRNA function in animals. The absence of functional TBC-11 leads to the persistent activation of RAB-6, which increases the localization of miRNA-unloaded Argonaute ALG-1 on endomembranes. This inactive form of Argonaute accumulates on polysomes, leading to defective miRNA-mediated target mRNA repression. Together, our results establish the importance of intracellular trafficking for miRNA function and demonstrates the involvement of a small GTPase in proper Argonaute localization in vivo.
2021-03-16 | GSE141719 | GEO