Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Post-translational Modification of RNA m6A Demethylase ALKBH5 Regulates ROS-induced DNA Damage Response

ABSTRACT: Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find that ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating ALKBH5 post-translational modifications (PTMs), leading to the rapid and efficient induction of thousands of genes involved in a variety of biological processes including DNA damage repair. Mechanistically, ROS promotes ALKBH5 SUMOylation through activating ERK/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Moreover, ERK/JNK/ALKBH5-PTMs/m6A axis is activated by ROS in hematopoietic stem/progenitor cells (HSPCs) in vivo in mice, suggesting a physiological role of this molecular pathway in the maintenance of genome stability in HSPCs. Together, our study uncovers a molecular mechanism involving ALKBH5 PTMs and increased mRNA m6A levels that protect genomic integrity of cells in response to ROS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE144620 | GEO | 2021/04/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

m6A Demethylase ALKBH5 attenuates doxorubicin-induced cardiotoxicity via posttranscriptional stabilization of Rasal3

Project description:The clinical application of anthracyclines such as doxorubicin (DOX) is limited due to their cardiotoxicity. N6-methyladenosine (m6A) plays an essential role in numerous biological processes. However, the roles of m6A and m6A demethylase ALKBH5 in DOX-induced cardiotoxicity (DIC) remain unclear. In this research, DIC models were constructed using Alkbh5-knockout (KO), Alkbh5-knockin (KI), and Alkbh5-myocardial-specific knockout (ALKBH5flox/flox, αMyHC-Cre) mice. Cardiac function and DOX-mediated signal transduction were investigated. As a result, both Alkbh5 whole-body KO and myocardial-specific KO mice had increased mortality, decreased cardiac function, and aggravated DIC injury with severe myocardial mitochondrial damage. Conversely, ALKBH5 overexpression alleviated DOX-mediated mitochondrial injury, increased survival, and improved myocardial function. Mechanistically, ALKBH5 regulated the expression of Rasal3 in an m6A-dependent manner through posttranscriptional mRNA regulation and reduced Rasal3 mRNA stability, thus activating RAS3, inhibiting apoptosis through the RAS/RAF/ERK signaling pathway, and alleviating DIC injury. These findings indicate the potential therapeutic effect of ALKBH5 on DIC.

2023-03-08 | GSE224215 | GEO

Chromatin state maintains human myeloid leukemia by regulating m6A demethylase ALKBH5 expression [RNA-Seq]

Project description:ALKBH5 is the RNA N(6)-methyladenosine (m6A) demethylase. To under sthand the function and mechnism of ALKBH5 in human acute myeloid leukemia, we compared the m6A profiling in wild-type, ALKBH5-knock-down, and ALKBH5 rescue THP1 cells.

2020-05-27 | GSE128574 | GEO

Chromatin state maintains human myeloid leukemia by regulating m6A demethylase ALKBH5 expression [m6A-seq]

2020-05-27 | GSE128520 | GEO

RNA demethylase ALKBH5 promotes tumorigenesis in multiple myeloma [m6A-seq]

Project description:We here report ALKBH5, a m6A RNA demethylase, as a crucial oncogene in multiple myeloma (MM). Using various MM models, we demonstrated a critical requirement of ALKBH5 for MM cell proliferation in vitro and in vivo. To identify the potential mRNA targets of ALKBH5, we conducted m6A-seq with mRNA samples enriched from MM cells with or without ALKBH5 knockdown.

2022-07-07 | GSE180207 | GEO

Chromatin state maintains human myeloid leukemia by regulating m6A demethylase ALKBH5 expression [Ribo-seq]

Project description:ALKBH5 is the RNA N(6)-methyladenosine (m6A) demethylase. To understhand the function and mechnism of ALKBH5 in human acute myeloid leukemia, we compared the translational efficiency in wild-type and ALKBH5-knock-down THP1 cells.

2020-05-27 | GSE146849 | GEO

ALKBH5 facilitates the progression of skin cutaneous melanoma through promoting ABCA1 demethylation and inhibiting autophagy in an m6A-dependent manner

Project description:Background: N6-methyladenosine (m6A) is the most common and abundant mRNA modification, playing an essential role in biological processes and tumor development. However, the role of m6A methylation in skin cutaneous melanoma (SKCM) is not yet clear. This study analyzed the expression of m6A-related functional genes in SKCM and aimed to explore the key demethylase ALKBH5 mediated m6A modification and its potential mechanism in human SKCM. Methods: Based on public databases, the m6A-related gene expression landscape in SKCM was portrayed. MeRIP-Seq and RNA-Seq were used to recognize the downstream target of ALKBH5. In vivo and in vitro functional phenotype and rescue functional experiments were performed to explore the mechanism of the ALKBH5-ABCA1 axis in SKCM. Results: We found ALKBH5 upregulated in SKCM, associated with poor prognosis. ALKBH5 can promote melanoma cell proliferation, colony formation, migration, and invasion and inhibit autophagy in vitro, facilitating tumor growth and metastasis in vivo. We identified ABCA1, a membrane protein that assists cholesterol efflux, as a downstream target of ALKBH5-mediated m6A demethylation. Finally, our data demonstrated that ALKBH5 promoted SKCM via mediating ABCA1 downregulation by reducing ABCA1 mRNA stability in an m6A-dependent manner. Conclusion: Our findings exhibited the functional value of the key demethylase ALKBH5 mediated m6A modification in the progression of SKCM, suggesting ALKBH5 and its target ABCA1 as potential therapeutic targets in SKCM.

2024-02-29 | GSE253795 | GEO

Chromatin state maintains human myeloid leukemia by regulating m6A demethylase ALKBH5 expression [Slam-seq]

Project description:ALKBH5 is the RNA N(6)-methyladenosine (m6A) demethylase. To understhand the function and mechnism of ALKBH5 in human acute myeloid leukemia, we compared the RNA decay rate in wild-type and ALKBH5-knock-down THP1 cells.

2020-05-27 | GSE146874 | GEO

Chromatin state maintains human myeloid leukemia by regulating m6A demethylase ALKBH5 expression [ATAC-seq]

Project description:ALKBH5 is the RNA N(6)-methyladenosine (m6A) demethylase. To understhand the function and mechnism of ALKBH5 in human acute myeloid leukemia, we compared the translational efficiency in wild-type and ALKBH5-knock-down MOLM-13 cells.

2020-05-27 | GSE146831 | GEO

ALKBH5 cooperated with LINC00659 promote gastric cancer progression by JAK1 mRNA m6A-YTHDF2-dependent modification

Project description:N6-methyladenosine (m6A) modification is the most prevalent RNA epigenetic regulation in eukaryotic cells. Recent studies focused on the association between m6A and non-coding RNAs. The demethylase ALKBH5 acts as critical oncogenes or tumor suppressors through multiple mechanisms in various cancers. Here, we find that ALKBH5 is highly expressed in GC tissues and is associated with poor prognosis. ALKBH5 promoted the proliferation and metastasis both in vitro and in vivo. ALKBH5 was recruited by LINC00659, which removed m6A modifications of JAK1, leading to the upregulated expression of JAK1.Since ALKBH5 and LINC00659 have oncogenic role in gastric cancer (GC) progression with poor prognosis, ALKBH5-LINC00659/m6A/JAK1 axis can be new biological mechanisms behind GC development and future therapeutic opportunities.

2024-08-17 | GSE182544 | GEO

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