Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Passive shaping of intra- and intercellular m6A dynamics via mRNA metabolism

ABSTRACT: m6A is the most widespread mRNA modification and is primarily implicated in controlling mRNA stability. Fundamental questions pertaining to m6A are the extent to which it is dynamically modulated within cells and across stimuli, and the forces underlying such modulation. Prior work has focused on investigating active mechanisms governing m6A levels, such as recruitment of m6A writers or erasers leading to either ‘global’ or ‘site-specific’ modulation. Here, we propose that changes in m6A levels across subcellular compartments and biological trajectories may result from passive changes in gene-level mRNA metabolism. To predict the intricate interdependencies between m6A levels, mRNA localization, and mRNA decay, we establish a differential model ‘m6ADyn’ encompassing mRNA transcription, methylation, export, and m6A-dependent and independent degradation. We validate the predictions of m6ADyn in the context of intracellular m6A dynamics, where m6ADyn predicts associations between relative mRNA localization and m6A levels, which we experimentally confirm. We further explore m6ADyn predictions pertaining to changes in m6A levels upon controlled perturbations of mRNA metabolism, which we also experimentally confirm. Finally, we demonstrate the relevance of m6ADyn in the context of cellular heat stress response, where genes subjected to altered mRNA product and export also display predictable changes in m6A levels, consistent with m6ADyn predictions. Our findings establish a framework for dissecting m6A dynamics and suggest the role of passive dynamics in shaping m6A levels in mammalian systems.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE272629 | GEO | 2024/07/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Passive shaping of intra- and intercellular m6A dynamics via mRNA metabolism

Project description:Passive shaping of intra- and intercellular m6A dynamics via mRNA metabolism

| PRJNA1137857 | ENA

Co-effects of m6A dynamics and chromatin accessibility changes regulate cardiomyocyte differentiation

Project description:The growth and differentiation of cardiomyocytes are primarily driven by gene expression dynamics, with various epigenetic modifications playing a crucial role in this process. One of the most common modifications on mRNA, m6A, influences the regulation of mRNA metabolism; however, its function remains enigmatic. In this study, we identified a correlation between m6A modification and cardiomyocyte differentiation by profiling m6A dynamics during the transition of pluripotent stem cells into cardiomyocytes. Although the overall m6A modification level remains relatively stable, most genes exhibit changes in their m6A levels as cardiomyocyte differentiation progresses. We observed that alterations in chromatin accessibility can impact the binding capabilities of m6A writers, erasers, and readers, consequently affecting m6A levels. Furthermore, the coordinated changes of m6A and chromatin accessibility are closely associated with early-stage cardiomyocyte differentiation. These findings suggest that m6A is a significant factor in determining the fate of cardiomyocyte differentiation, shedding light on its role in this critical process.

2023-08-24 | GSE231549 | GEO

The m 6 A-methylase complex recruits TREX and regulates mRNA export.

Project description:N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA. This modification has previously been shown to alter the export kinetics for mRNAs though the molecular details surrounding this phenomenon remain poorly understood. Here we show that the m6A complex (WTAP, KIAA1429, METTL3/14) drives recruitment of the TREX mRNA export complex onto m6A modified mRNAs and this process is essential for the efficient export of certain mRNAs. Depletion of the core m6A complex leads to loss of TREX from mRNAs which undergo the m6A modification. We show that TREX stimulates recruitment of the m6A reader protein YTHDC1 to the mRNP and the m6A complex influences the interaction of TREX with YTHDC1. We suggest that m6A acts as a surrogate for other TREX recruitment mechanisms such as splicing and 5’ capping, in long internal and final exons which may otherwise be devoid of this essential complex for mRNA export.

2018-10-03 | GSE111878 | GEO

ALKBH5 is a New Mammalian RNA Demethylase

Project description:N6-methyladenosine (m6A) is the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Here we report ALKBH5 as a new mammalian demethylase that oxidatively removes the m6A modification in mRNA in vitro and inside cells. This demethylation activity of ALKBH5 significantly affects mRNA export and RNA metabolism as well as the assembly of mRNA processing factors in nuclear speckles. Alkbh5-deficient male mice are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. In accordance with this defect, we have identified in mouse testes 1552 differentially expressed genes which cover broad functional categories and include spermatogenesis-related mRNAs involved in the p53 functional interaction network. We show that Alkbh5-deficiency impacts the expression levels of some of these mRNAs, supporting the observed phenotype. The discovery of this new RNA demethylase strongly suggests that the reversible m6A modification plays fundamental and broad functions in mammalian cells. RNA-seq in two cell types

2013-02-15 | E-GEOD-40132 | biostudies-arrayexpress

The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export

Project description:The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export

| PRJNA482996 | ENA

Nuclear m6A Reader YTHDC1 Promotes Muscle Stem Cell Activation/Proliferation by Regulating mRNA Splicing and Nuclear Export [LACE-seq]

Project description:Nuclear m6A Reader YTHDC1 Promotes Muscle Stem Cell Activation/Proliferation by Regulating mRNA Splicing and Nuclear Export

2023-03-20 | GSE210126 | GEO

Nuclear m6A Reader YTHDC1 Promotes Muscle Stem Cell Activation/Proliferation by Regulating mRNA Splicing and Nuclear Export [RNA-seq]

Project description:Nuclear m6A Reader YTHDC1 Promotes Muscle Stem Cell Activation/Proliferation by Regulating mRNA Splicing and Nuclear Export

2023-03-20 | GSE210125 | GEO

RNA Seq of Fmr1 NPC nuclear fractions

Project description:N6-methyladenosine (m6A) modification of mRNA is emerging as a vital mechanism regulating RNA function. Here, we show that fragile X mental retardation protein (FMRP), an RNA-binding protein, reads m6A to regulate nuclear export of methylated mRNA targets during neural stem cell differentiation. In Fmr1 KO mice neural progenitors show delayed cell cycle exit and differentiation, resulting in their progressive accumulation in the ventricular and subventricular zones. RNA-seq of neural precursor cells (NPCs) from Fmr1 KO mice and m6A-seq uncovered nuclear retention of m6A-modified FMRP target mRNAs involved in regulating neural differentiation, including components of Notch and Hedgehog signaling pathways. Analysis of NPCs from Mettl14 cKO mice, which are devoid of m6A, revealed that methylation of RNAs promotes their nuclear export through CRM1. Altogether, our findings suggest that FMRP reads and facilitates nuclear export of m6A-modified mRNAs to regulate neural stem cell differentiation, contributing to Fragile X syndrome.

2019-07-23 | GSE121809 | GEO

N6-methyladenosine (m6A) profiling in 60 YRI LCLs

Project description:N6-methyladenosine (m6A), the most abundant messenger RNA (mRNA) modification, has emerged as a critical post-transcriptional mechanism that regulates various aspect of mRNA metabolism including pre-mRNA processing, mRNA export, mRNA stability and translation efficiency. However the genetics basis of m6A is largely unexplored. In this work, we mapped m6A-QTLs in 60 LCLs and used the resulting tens of thousands of QTLs to provide insights to m6A biology and its contribution to human complex trait.

2020-05-04 | GSE125377 | 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

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