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Effects of Dcp1a and Dcp2 knockdown during mouse oocyte maturation

ABSTRACT: Oocyte maturation is accompanied by a transition from mRNA stability to instability. We investigated the role of DCP1A and DCP2, proteins responsible for mRNA decapping, in mRNA destabilization during mouse oocyte maturation. siRNA-mediated knockdown of both Dcp1a and Dcp2 transcripts prior to initiation of maturation inhibited the maturation-associated increase of DCP1A and DCP2, stabilized a set of maternal mRNAs that are normally degraded during maturation, and inhibited development beyond the 2-cell stage, likely a consequence of failure to activate fully the zygotic genome.

ORGANISM(S): Mus musculus

PROVIDER: GSE27049 | GEO | 2013/02/06

SECONDARY ACCESSION(S): PRJNA137629

REPOSITORIES: GEO

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Effects of Dcp1a and Dcp2 knockdown during mouse oocyte maturation

Project description:Oocyte maturation is accompanied by a transition from mRNA stability to instability. We investigated the role of DCP1A and DCP2, proteins responsible for mRNA decapping, in mRNA destabilization during mouse oocyte maturation. siRNA-mediated knockdown of both Dcp1a and Dcp2 transcripts prior to initiation of maturation inhibited the maturation-associated increase of DCP1A and DCP2, stabilized a set of maternal mRNAs that are normally degraded during maturation, and inhibited development beyond the 2-cell stage, likely a consequence of failure to activate fully the zygotic genome. Total RNA from 30 MII eggs was used in each sample. Three independent biological replicates were analyzed for each condition.

2013-02-06 | E-GEOD-27049 | biostudies-arrayexpress

mRNA sequencing analysis of zebrafish embryos, Dcp2 inhibition

Project description:we determined the contribution of the decapping enzyme Dcp2 to maternal mRNA clearance in zebrafish embryos by overexpressing a dominant-negative form of Dcp2.

2017-05-31 | GSE95679 | GEO

mRNA decapping factors and the exonuclease Xrn2 function in widespread premature termination of RNA polymerase II transcription

Project description:We report a function of human mRNA decapping factors in control of transcription by RNA polymerase II. Decapping proteins Edc3, Dcp1a and Dcp2 and the termination factor TTF2 co-immunoprecipitate with Xrn2, the nuclear 5'-3' exonuclease torpedo that facilitates transcription termination at the 3' ends of genes. Dcp1a, Xrn2 and TTF2 localize near transcription start sites (TSSs) by ChIP-Seq. At genes with 5' peaks of paused pol II, knockdown of decapping or termination factors, Xrn2 and TTF2, shifted polymerase away from the TSS toward upstream and downstream distal positions. This re-distribution of pol II is similar in magnitude to that caused by depletion of the elongation factor Spt5. We propose that coupled decapping of nascent transcripts and premature termination by the torpedo mechanism is a widespread mechanism that limits bidirectional pol II elongation. Regulated co-transcriptional decapping near promoter-proximal pause sites followed by premature termination could control productive pol II elongation. RNA pol II (GSE30895: GSM766171), Xrn2, TTF2 and Dcp1a were localized by ChIP-Seq in HeLa cells. RNA pol II was localized in control HEK293 cells and cells infected with lentiviruses expressing a scrambled control shRNA (scr), and shRNAs targeting the following proteins: Xrn2, TTF2, Xrn2+TTF2, Edc3, Dcp1a, and Dcp2.

2012-04-04 | E-GEOD-36185 | biostudies-arrayexpress

Cordycepin Delays Postovulatory Aging of Mammalian Oocytes through Inhibition of Maternal mRNAs Degradation via DCP1A Polyadenylation Suppression

Project description:Postovulatory aging leads to the decline in oocyte quality and subsequent impairment of embryonic development, thereby reducing the success rates of assisted reproductive technology (ART). Nevertheless, potential preventative strategies to improve aging oocytes quality and the associated underlying mechanisms warrant further investigation. In this study, we identify cordycepin, an natural nucleoside analogue, as having the potential to restore the postovulatory aging-induced decline in oocyte quality, including aspects such as oocyte fragmentation, embryonic developmental competence, spindle/chromosomes morphology and mitochondrial function. Proteomic and RNA sequencing analyses revealed that cordycepin inhibited the degradation of several crucial maternal proteins and mRNAs caused by aging. Mechanistically, cordycepin was found to suppress the elevation of DCP1A protein levels by inhibiting polyadenylation during postovulatory aging, consequently impeding the decapping of maternal mRNAs. In humans, the increased degradation of DCP1A and total mRNA during aging was also inhibited by cordycepin. Collectively, our findings demonstrate that cordycepin may prevent postovulatory aging of mammalian oocytes by inhibition of maternal mRNAs degradation via DCP1A polyadenylation suppression, thereby promoting the successful rates of ART procedure.

2024-01-26 | PXD042600 | Pride

Mus musculus

Project description:Effects of Dcp1a and Dcp2 knockdown during mouse oocyte maturation

| PRJNA137629 | ENA

mRNA decapping factors and the exonuclease Xrn2 function in widespread premature termination of RNA polymerase II transcription

2012-04-05 | GSE36185 | GEO

YTHDF2 regulates maternal transcriptome degradation and embryo development in goat

Project description:Little information is known regarding the maternal mRNA clearance and mechanisms behind it in farm animals. In the present study, we determined 3362 differentially expressed genes as the maternal mRNAs in goat using RNA-seq. We further reported that knockdown of YTHDF2 led to decreased blastocyst rate and impaired the maternal mRNAs clearance by downregulation of decapping enzymes DCP1A and DCP2, and the de-adenlyase CNOT1 and CNOT11.

2020-08-27 | GSE156924 | GEO

The IkB kinase complex is a regulator of mRNA stability

Project description:The IkB kinase (IKK) is considered to control gene expression primarily through activation of the transcription factor NF-kB. However, we show here that IKK additionally regulates gene expression on post-transcriptional level. IKK interacted with several mRNA binding proteins, including a (P)-body scaffold protein, termed Enhancer of Decapping 4 (EDC4). IKK bound to and phosphorylated EDC4 in a stimulus-sensitive manner, leading to co-recruitment of P-body components, mRNA Decapping Proteins 1a and 2 (DCP1a and DCP2) and to an increase in P-body numbers. Using RNA sequencing, we identified scores of transcripts whose stability was regulated via the IKK-EDC4 axis. Strikingly, in the absence of stimulus IKK-EDC4 promoted destabilization of pro-inflammatory cytokines and regulators of apoptosis. Our findings expand the reach of IKK beyond its canonical role as a regulator of transcription.

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Global RNA stability profiling during selective chemical inhibition of human Dcp2

Project description:Multiple RNA decapping enzymes coexist in mammalian cells to regulate decay of partially overlapping sets of cellular transcripts, but a comprehensive understanding of cellular substrate selectivity of each enzyme is yet to be achieved. Previously we demonstrate the utility of TimeLapse-seq in global profiling of RNA stability changes in human Dcp2 knockout cells. However, secondary transcriptional changes and upregulation of alternative decay pathways have obscured complete mapping of Dcp2 substrates. Here, we present the discovery and first application of a cell-permeable, highly selective Dcp2 ligand in the chemical genetic study of its RNA substrates.

2020-12-16 | GSE153258 | GEO

Decapping factor Dcp2 controls mRNA abundance and translation to adjust metabolism and filamentation to nutrient availability

Project description:Degradation of most yeast mRNAs involves decapping by Dcp1/Dcp2. DEAD-box protein Dhh1 has been implicated as an activator of decapping, and as a translational repressor, but their functions in cells are incompletely understood. We have analyzed these questions by a combination of ribosome profiling, RNA-Seq, CAGE analysis of capped mRNAs.

2023-02-07 | GSE216831 | GEO

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