Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mettl3/m6A promotes translation of pathogenic mRNAs to mediate cystogenesis in mouse models of ADPKD

ABSTRACT: Purpose: Determine the differential m6A methylation pattern of Mettl3 between wildtype, Pkd1F/RC-KO and Pkd1F/RC-Mettl3-DKO mouse kidneys. Methods: m6A RNA IP using the Magna MeRIP™ m6A Kit (EMD Millipore, catalog #17-10499) was performed on P18 wildtype, Pkd1F/RC-KO and Pkd1F/RC-Mettl3-DKO mouse kidney samples. Two biological replicate samples from each genotype were sequenced. Each sample was a pool of 6 kidneys of the same genotype. The input samples were also sequenced to obtain mRNA profiles. Results: 133 mRNAs were found to be differentially hypermethylated in the Pkd1-KO kidneys compared to the control kidneys and differentially hypomethylated in the Pkd1-Mettl3-DKO kidneys compared to the Pkd1-KO kidneys. Two key pathogenic mRNAs namely, c-Myc and Avpr2 were identified and validated as Mettl3 targets. The mRNA transcript levels were unchanged between Pkd1-KO and Pkd1-Mettl3-DKO kidneys. Conclusion: Mettl3/m6A promotes translation of pathogenic mRNAs to mediate cystogenesis in mouse models of ADPKD.

ORGANISM(S): Mus musculus

PROVIDER: GSE165956 | GEO | 2021/02/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

m6A RNA Methylation is Critical for Adequate Exit from Naïve Pluripotency and Execution of Mammalian Development (Ribo-seq)

Project description:In this study we identify Mettl3, an m6A RNA modification writer, as a critical regulator for terminating naïve pluripotency and a positive maintainer of primed pluripotency in vitro and in vivo. Remarkably, Mettl3 knockout pre-implantation epiblasts and naïve ES cells, entirely lack m6A on coding mRNAs and are viable. Yet, they fail to adequately terminate the naïve pluripotent state, and subsequently undergo aberrant priming and early lineage commitment at the post-implantation stage. A comprehensive functional and genomic analysis involving profiling of m6A, RNA transcription and translation in Mettl3 wild-type and knockout pluripotent and differentiated cells, identified m6A as a critical determinant that destabilizes secondary naïve specific pluripotency genes Esrrb, Klf4 and Nanog, and restrains their transcript stability and translation efficiency. In summary, our findings provide for the first time evidence for a critical role for an mRNA epigenetic modification in early mammalian development in vivo, and identify a mechanism that functionally regulates mouse naïve and primed pluripotency in an opposing manner. Ribosome footprint (Ribo-Seq) was measured from mouse embryonic stem cells and mouse embriod bodies, in WT and Mettl3-KO cell lines.

2014-11-02 | E-GEOD-61996 | biostudies-arrayexpress

Effect of global Caspase-1 (Casp1) knockout (KO) on kidney gene expression in an orthologous mouse model of polycystic kidney disease (PKD)

Project description:We examined the effects of global Caspase-1 KO on kidney gene expression in an orthologous mouse model of PKD, which carries a homozygous knockin missense mutation, Pkd1RC/RC , that matches a human disease allele, PKD1 p.R3277C ("RC").

2022-09-30 | GSE207957 | GEO

m6A RNA Methylation is Critical for Adequate Exit from NaM-CM-/ve Pluripotency and Execution of Mammalian Development (3p-Seq)

Project description:In this study we identify Mettl3, an m6A RNA modification writer, as a critical regulator for terminating naM-CM-/ve pluripotency and a positive maintainer of primed pluripotency in vitro and in vivo. Remarkably, Mettl3 knockout pre-implantation epiblasts and naM-CM-/ve ES cells, entirely lack m6A on coding mRNAs and are viable. Yet, they fail to adequately terminate the naM-CM-/ve pluripotent state, and subsequently undergo aberrant priming and early lineage commitment at the post-implantation stage. A comprehensive functional and genomic analysis involving profiling of m6A, RNA transcription and translation in Mettl3 wild-type and knockout pluripotent and differentiated cells, identified m6A as a critical determinant that destabilizes secondary naM-CM-/ve specific pluripotency genes Esrrb, Klf4 and Nanog, and restrains their transcript stability and translation efficiency. In summary, our findings provide for the first time evidence for a critical role for an mRNA epigenetic modification in early mammalian development in vivo, and identify a mechanism that functionally regulates mouse naM-CM-/ve and primed pluripotency in an opposing manner. 3' polyA RNA-sequencing (equivalent to Digital Gene Expression) measured in mouse Embryonic Stem Cells (ESCs) and mouse Embriod bodies (EBs) 0,4 & 8 hours after treatment with Actinomycin which halts transcription. Measured in both WT and Mettl3-KO cells.

2014-11-02 | E-GEOD-61994 | biostudies-arrayexpress

m6A RNA Methylation is Critical for Adequate Exit from Naïve Pluripotency and Execution of Mammalian Development (RNA-Seq)

Project description:In this study we identify Mettl3, an m6A RNA modification writer, as a critical regulator for terminating naïve pluripotency and a positive maintainer of primed pluripotency in vitro and in vivo. Remarkably, Mettl3 knockout pre-implantation epiblasts and naïve ES cells, entirely lack m6A on coding mRNAs and are viable. Yet, they fail to adequately terminate the naïve pluripotent state, and subsequently undergo aberrant priming and early lineage commitment at the post-implantation stage. A comprehensive functional and genomic analysis involving profiling of m6A, RNA transcription and translation in Mettl3 wild-type and knockout pluripotent and differentiated cells, identified m6A as a critical determinant that destabilizes secondary naïve specific pluripotency genes Esrrb, Klf4 and Nanog, and restrains their transcript stability and translation efficiency. In summary, our findings provide for the first time evidence for a critical role for an mRNA epigenetic modification in early mammalian development in vivo, and identify a mechanism that functionally regulates mouse naïve and primed pluripotency in an opposing manner. polyA RNA-seq was measured in mouse embryonic stem cells (ESCs) and embroid bodies (EBs), each in WT and in Mettl3-KO cell lines. RNA-seq was measured also from WT mouse embronic fibroblasts (MEF). 3 biological replicates are available from ESCs and 2 from EBs. Replicate C in ESCs was measured alongside protein levels (SILAC) and was used for the analysis of that assay.

2014-11-02 | E-GEOD-61997 | biostudies-arrayexpress

Gene expression profiling of kidneys derived from Pkd1 conditional knock-out (KO) mice treated by Salsalate

Project description:Computational identification of gene expression pathways and key regulatory factors in the Pkd1 KO kidneys treated by Salsalate

2019-10-03 | GSE126454 | GEO

RNA methylation destabilizes developmental regulators in murine embryonic stem cells (m6A)

Project description:m6A-seq of mouse embryonic stem cell wildtype or mutant depleted of Mettl3 or Mettl14 m6A-mRNA library for mouse embryonic stem cell each having one biological replicate were generated using HiSeq2000 v3 flowcell (Illumina) and sequenced for 100 bases with separate 7 base indexing read in a single lane.

2014-01-06 | E-GEOD-46878 | biostudies-arrayexpress

Gene expression profiling of kidneys derived from Pkd1 conditional knock-out (KO) mice treated by salsalate, tolvaptan, and in combination

Project description:Computational identification of gene expression pathways or key regulatory factors in the Pkd1 KO kidneys treated by salsalate, tolvaptan, and in combination

2023-01-16 | GSE198340 | GEO

m6A RNA Methylation Is Regulated by MicroRNAs and Promotes Reprogramming to Pluripotency

Project description:N6-methyladenosine (m6A) has been recently identified as a conserved epitranscriptomic modification of eukaryotic mRNAs, but its features, regulatory mechanisms, and functions in cell reprogramming are largely unknown. Here, we report m6A modification profiles in the mRNA transcriptomes of four cell types with different degrees of pluripotency. Comparative analysis reveals several features of m6A, especially gene- and cell-type-specific m6A mRNA modifications. We also show that microRNAs (miRNAs) regulate m6A modification via a sequence pairing mechanism. Manipulation of miRNA expression or sequences alters m6A modification levels through modulating the binding of METTL3 methyltransferase to mRNAs containing miRNA targeting sites. Increased m6A abundance promotes the reprogramming of mouse embryonic fibroblasts (MEFs) to pluripotent stem cells; conversely, reduced m6A levels impede reprogramming. Our results therefore uncover a role for miRNAs in regulating m6A formation of mRNAs and provide a foundation for future functional studies of m6A modification in cell reprogramming. m6A-seq in ESC, iPSC, NSC and sertoli cells.

2015-03-10 | E-GEOD-52125 | biostudies-arrayexpress

RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs (ChIP-Seq 3)

Project description:N6-methyladenosine (m6A) methyltransferase METTL3 mainly mediates mRNA m6A methylation and plays important roles in various biological processes. Here we report a chromatin-based role for METTL3 in heterochromatin integrity regulation in mouse embryonic stem cells (mESCs). We show that in mESCs METTL3 predominantly localizes to one of the most active endogenous retroviruses (ERVs) families, the intracisternal A-type particles (IAPs). We further show that METTL3 knockout (KO) impairs deposition of multiple heterochromatin marks on METTL3-targeted IAPs, and upregulates IAP transcription without affecting the stability of the resulting RNAs. De-repression can be rescued by wildtype but not catalytically inactive METTL3, suggesting that METTL3-mediated methylation is important for heterochromatin silencing. Mechanistically, we demonstrate that METTL3 physically interacts with the H3K9 tri-methyltransferase SETDB1 and its regulator TRIM28, and reciprocally promote each other’s localization to IAPs. Importantly, we show that m6A catalytical activity of METTL3 is necessary for its own recruitment to chromatin but not its interactions with SETDB1 and TRIM28. Taken together, our findings demonstrate that RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs.

2020-12-09 | GSE160103 | GEO

RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs [YTHDC1_ChIRP-Seq]

2020-12-09 | GSE145134 | GEO