Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Roles of Mettl14 in mouse limb bud development

ABSTRACT: m6A regulates virtually every step in RNA metabolism. However, its toles in limb development remains largely unknown. To understand the roles, we created a limb bud-specific conditional knockout (cKO) mice and control heterozygous (cHet) mice of the Mettl14 gene, which encodes an essential subunit in the m6A methyltransferase complex METTL3/METTL14. We harvested limb buds from the mice on E12.5 and applied the proteins to quantitative mass spectrometry to understand how the depletion of Mettl14 affected the proteomes.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Embryo

SUBMITTER: Nobuaki Kikyo

LAB HEAD: Nobuaki Kikyo

PROVIDER: PXD049092 | Pride | 2025-04-03

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	18139_tc_d950_F1A_ee02704.mzIdentML	Mzid
	18139_tc_d950_F1A_ee02704.raw	Raw
	18140_tc_d950_F2A_ee02705.mzIdentML	Mzid
	18140_tc_d950_F2A_ee02705.raw	Raw
	18141_tc_d950_F3A_ee02706.mzIdentML	Mzid

Items per page:

1 - 5 of 24

Similar Datasets

METTL14 regulates chondrogenesis through the GDF5–RUNX–extracellular matrix gene axis during limb development [m6A-seq]

Project description:METTL14 forms a protein complex that induces m6A methylation on RNA but its roles in mouse limb development remains elusive. We knocked out Mettl14 in a limb bud-specific manner with the Prx1 promoter-driven Cre. The resulting Prx1-cre;Mettl14 flox/flox (conditional KO or cKO) mice showed shorter limbs with disrupted bone and cartilage development compared with the heterozygous Prx1-cre;Mettl14 wild type/flox (cHet) control mice. To understand the molecular basis for the abnormalities, we applied total RNA from day 12.5 (E12.5) embryonic limb buds to m6A-seq.

2025-04-03 | GSE271890 | GEO

METTL14 regulates chondrogenesis through the GDF5–RUNX–extracellular matrix gene axis during limb development [scRNA-seq]

Project description:Mettl14 forms a protein complex that induces m6A methylation on RNA but its roles in mouse limb development remains elusive. Here, the Mettl14 gene was knocked out in a limb bud-specific manner in Mettl14 flox/flox mice with the Prx1 promoter-driven cre. Dissociated cells from day 12.5 (E12.5) embryonic limb buds were applied to scRNA-seq to identify differentially expressed genes in a cell type-specific manner. Samples prepared from Per1cre;Mettl14 wild type/flox and Per1cre;Mettl14 flox/flox mice were labeled as cHet and cKO, respectively.

2025-04-03 | GSE253124 | GEO

Widespread N6-methyladenosine-dependent RNA Structural Switches Regulate RNA-Protein Interactions

Project description:We show that N6-methyladenosine (m6A), the most abundant internal modification in mRNA/lncRNA with still poorly characterized function, alters RNA structure to facilitate the access of RBM for heterogeneous nuclear ribonucleoprotein C (hnRNP C). We term this mechanism m6A-switch. Through combining PAR-CLIP with Me-RIP, we identify 39,060 m6A-switches among hnRNP C binding sites transcriptome-wide. We show that m6A-methyltransferases METTL3 or METTL14 knockdown decreases hnRNP C binding at 16,582 m6A-switches. Taken together, 2,798 m6A-switches of high confidence are identified to mediate RNA-hnRNP C interactions and affect diverse biological processes including cell cycle regulation. These findings reveal the biological importance of m6A and provide insights into the sophisticated regulation of RNA-RBP interactions through m6A-induced RNA structural remodeling. Measure the m6A methylated hnRNP C binding sites transcriptome-wide by PARCLIP-MeRIP; measure the differential hnRNP C occupancies upon METTL3/METTL14 knockdown by PAR-CLIP; measure RNA abundance and splicing level changes upon HNRNPC, METTL3 and METTL14 knockdown

2015-02-27 | E-GEOD-56010 | biostudies-arrayexpress

METTL14 regulates chondrogenesis through the GDF5–RUNX–extracellular matrix gene axis during limb development [RNA-seq]

Project description:METTL14 forms a protein complex that induces m6A methylation on RNA but its roles in mouse limb development remains elusive. We knocked out Mettl14 in a limb bud-specific manner with the Prx1 promoter-driven Cre. The resulting Prx1-cre;Mettl14 flox/flox (conditional KO or cKO) mice showed shorter limbs with disrupted bone and cartilage development compared with the heterozygous Prx1-cre;Mettl14 wild type/flox (cHet) control mice. To understand the molecular basis for the abnormalities, we analyzed polysome RNA prepared from day 12.5 (E12.5) embryonic limb buds with RNA-seq.

2025-04-03 | GSE273285 | GEO

Cancer Mutations Rewire the RNA Methylation Specificity of METTL3-METTL14

Project description:Chemical modification of RNAs is important for post-transcriptional gene regulation. The METTL3-METTL14 complex generates most N6-methyladenosine (m6A) modifications in mRNAs, and dysregulated methyltransferase expression has been linked to numerous cancers. Here we show that m6A modification location, rather than the overall modification level, can impact oncogenesis. A gain-of-function missense mutation found in cancer patients, METTL14R298P, promotes malignant cell growth in culture and in transgenic mice. The mutant methyltransferase preferentially modifies noncanonical sites and transforms gene expression without increasing global m6A levels in mRNAs. The altered substrate specificity is intrinsic to METTL3-METTL14, helping us to propose a structural model for how the METTL3-METTL14 complex detects RNA sequences. Together, our work highlights that m6A location is important for function and that noncanonical methylation sites may impact aberrant gene expression and oncogenesis.

2024-12-21 | PXD039447 | Pride

Uncoupling Metabolic Health from Thermogenesis via BCAA Flux in Brown Fat

Project description:Brown adipose tissue (BAT) is best known for thermogenesis. Whereas numerous studies in rodents found tight associations between the metabolic benefits of BAT and enhanced whole-body energy expenditure, emerging evidence in humans suggests that BAT is protective against Type 2 diabetes independent of body-weight. The underlying mechanism for this dissociation remained unclear. Here, we report that impaired mitochondrial flux of branched-chain amino acids (BCAA) in BAT, by deleting mitochondrial BCAA carrier (MBC, encoded by Slc25a44), was sufficient to cause systemic insulin resistance without affecting whole-body energy expenditure or body-weight. We found that brown adipocytes catabolized BCAAs in the mitochondria as essential nitrogen donors for the biosynthesis of glutamate, N-acetylated amino acids, and one of the products, glutathione. BAT-selective impairment in mitochondrial BCAA flux led to elevated oxidative stress and insulin resistance in the liver, accompanied by reduced levels of BCAA-nitrogen derived metabolites in the circulation. In turn, supplementation of glutathione restored insulin sensitivity of BAT-specific MBC knockout mice. Notably, a high-fat diet rapidly impaired BCAA catabolism and the synthesis of BCAA-nitrogen derived metabolites in the BAT, while cold-induced BAT activity is coupled with an active synthesis of these metabolites. Together, the present work uncovers a mechanism through which brown fat controls metabolic health independent of thermogenesis via BCAA-derived nitrogen carriers acting on the liver.

2024-02-15 | PXD043992 | Pride

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

Primarily Dissecting the Autonomous and Cooperative Functions of METTL3 and METTL14 in mRNA Modification and Tumor Progression

Project description:METTL3 and METTL14 are considered to faithfully form the m6A writing complex in a 1:1 ratio, regulating the fate of mRNA by adding m6A modifications. However, recent studies have shown inconsistent expression and prognostic value of METTL3 and METTL14 in some tumors, suggesting that they may not be faithful in tumors. Pan-cancer analysis based on TCGA data reveals significant differences in expression, function, tumor burden correlation, and immune correlation between METTL3 and METTL14, especially in esophageal squamous cell carcinoma (ESCC). Knockdown of METTL3 significantly inhibits the cell proliferation in vitro and in vivo in ESCC EC109 cells, while the impact of METTL14 knockdown on proliferation is limited, and it cannot abolish the expression of METTL3 protein. mRNA-seq results indicate that METTL3 independently regulates the expression of 1615 genes, while only 776 genes are co-regulated by METTL3 and METTL14. Furthermore, through immunofluorescence co-localization, it is observed that METTL3 and METTL14 have certain inconsistencies in cellular localization. HPLC-MS results show that METTL3 independently binds to the Nop56p-associated pre-rRNA complex and mRNA splicing complex, separate from METTL14. Through bioinformatics and various omics studies, we have preliminarily discovered that METTL3 independently regulating tumor cell proliferation, and the participation in mRNA splicing may be a critical molecular mechanism. Our study provides an experimental basis and theoretical foundation for further understanding of the m6A writing complex and tumor therapy targeting METTL3.

2024-02-01 | PXD048886 | Pride

Proteome remodeling in LUC7L2-depleted and galactose-grown cells

Project description:Study of the proteome of K562 LUC7L2WT and LUC7L2KO cells grown for 14 days in DMEM media containing either 25mM glucose or 25mM galactose.

2021-04-12 | PXD021917 | Pride

RNA methylation destabilizes developmental regulators in murine embryonic stem cells (MoGene-2)

Project description:Recent methylome studies have located N6-methyladenosine (m6A) RNA modification on thousands of mammalian transcripts. However, its functional mechanism remains unclear. In this study, we examined the role of m6A methylation in mouse embryonic stem cells. To gain an understanding of dynamic changes in cells depleted with (proposed) methyltranferases at molecular level, we examined the time-series gene expression pattern in mESC lines using microarray analysis. After 0, 4 and 8 h incubation with scramble, shRNA for Mettl3 or Mettl14, mESC cells were collected and RNAs were isolated for microarray analysis using Affymetrix Genechip Mouse Gene 2.0 ST array. After 0 h incubation with scramble, shRNA for Mettl3 or Mettl14, mESC cells were collected and RNAs were isolated for microarray analysis using Affymetrix Genechip Mouse Gene 2.0 ST array.

2014-01-06 | E-GEOD-46879 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data