Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates epithelial cells senescence during 1-nitropyrene-induced pulmonary fibrosis [RNA-seq]

ABSTRACT: Abstract：Our previous study found that 1-nitropyrene (1-NP) exposure evoked pulmonary fibrosis in mice. However, the exact mechanism remained elusive. We found that 1-NP induced telomere damage and cellular senescence in mice lungs and MLE-12 cells. Further research showed that 1-NP downregulated telomere repeat binding factor 2 (TRF2), and upregulated FBXW7. Mechanistically, 1-NP-caused TRF2 ubiquitination and proteasomal degradation depended on E3 ubiquitin ligase activity of FBXW7. Moreover, 1-NP upregulated FBXW7 m6A modification via an ALKBH5-YTHDF1-dependent manner. Further analysis found 1-NP promoted ALKBH5 SUMOylation and subsequent proteasomal degradation. Additionally, 1-NP evoked mitochondrial reactive oxygen species (mtROS) overproduction. Mito-TEMPO, a mitochondrial-targeted antioxidant, mitigated 1-NP-caused mtROS overproduction, ALKBH5 SUMOylation, FBXW7 m6A modification, TRF2 degradation and cellular senescence. Taken together, mtROS-initiated ALKBH5 SUMOylation and subsequent FBXW7 m6A modification is indispensable in TRF2 degradation and cellular senescence in pulmonary epithelial cells during 1-NP-induced pulmonary fibrosis. Our study provides target intervention measures towards 1-NP-evoked pulmonary fibrosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE251884 | GEO | 2023/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates epithelial cells senescence during 1-nitropyrene-induced pulmonary fibrosis [Ribo-seq]

Project description:Abstract：Our previous study found that 1-nitropyrene (1-NP) exposure evoked pulmonary fibrosis in mice. However, the exact mechanism remained elusive. We found that 1-NP induced telomere damage and cellular senescence in mice lungs and MLE-12 cells. Further research showed that 1-NP downregulated telomere repeat binding factor 2 (TRF2), and upregulated FBXW7. Mechanistically, 1-NP-caused TRF2 ubiquitination and proteasomal degradation depended on E3 ubiquitin ligase activity of FBXW7. Moreover, 1-NP upregulated FBXW7 m6A modification via an ALKBH5-YTHDF1-dependent manner. Further analysis found 1-NP promoted ALKBH5 SUMOylation and subsequent proteasomal degradation. Additionally, 1-NP evoked mitochondrial reactive oxygen species (mtROS) overproduction. Mito-TEMPO, a mitochondrial-targeted antioxidant, mitigated 1-NP-caused mtROS overproduction, ALKBH5 SUMOylation, FBXW7 m6A modification, TRF2 degradation and cellular senescence. Taken together, mtROS-initiated ALKBH5 SUMOylation and subsequent FBXW7 m6A modification is indispensable in TRF2 degradation and cellular senescence in pulmonary epithelial cells during 1-NP-induced pulmonary fibrosis. Our study provides target intervention measures towards 1-NP-evoked pulmonary fibrosis.

2023-12-31 | GSE251659 | GEO

ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates epithelial cells senescence during 1-nitropyrene-induced pulmonary fibrosis

Project description:ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates epithelial cells senescence during 1-nitropyrene-induced pulmonary fibrosis

| PRJNA1055612 | ENA

ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates epithelial cells senescence during 1-nitropyrene-induced pulmonary fibrosis [RNA-seq]

Project description:ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates epithelial cells senescence during 1-nitropyrene-induced pulmonary fibrosis [RNA-seq]

| PRJNA1055667 | ENA

ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates epithelial cells senescence during 1-nitropyrene-induced pulmonary fibrosis [Ribo-seq]

Project description:ALKBH5 SUMOylation-mediated FBXW7 m6A modification regulates epithelial cells senescence during 1-nitropyrene-induced pulmonary fibrosis [Ribo-seq]

| PRJNA1055023 | ENA

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

Project description: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.

2021-04-29 | GSE144620 | 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 interacted proteins of ALKBH5 and FTO identified by IP-mass

Project description:Since m6A demethylases (FTO and ALKBH5) have been reported to be involved in pre-mRNA splicing regulation, we hypothesized that dynamic m6A distribution during mRNA maturation might involve removal of m6A in internal exons by FTO or ALKBH5 accompanied by splicing factors. To explore this we performed pull-down assays coupled with protein mass spectrometry.

2022-12-09 | PXD038705 | Pride

RBM33 Acts as an m6A Reader Essential for ALKBH5-mediated m6A Demethylation and Head and Neck Squamous Carcinoma Tumorigenesis [RIP-seq]

Project description:Head and neck squamous cell carcinoma (HNSC) is one of the most common malignant cancers worldwide. However, it is always detected at an advanced stage because of a lack of biomarkers for early diagnosis. Here, we identify the RNA binding motif protein 33 (RBM33) is commonly up-regulated in HNSC and it is essential for tumorigenesis. Mechanistically, RBM33 is an m6A reader protein and forms a complex with ALKBH5. RBM33 plays crucial roles in ALKBH5-mediated mRNA m6A demethylation not only by recruitment ALKBH5 to substrate but also activation its demethylase activity through inhibition it’s SUMOylation. Moreover, global transcriptomic and epitranscriptomic analyses identify that DDIT4 is a functional downstream target gene for RBM33 in HNSC and RBM33-mediated HNSC tumorigenesis by inhibition the mTOR pathway through the inhibition of m6A-dependent DDIT4 mRNA decay. Taken together, our study uncovers a novel molecular mechanism that RBM33/ALKBH5/m6A/DDIT4/mTOR axis regulates HNSC progression through the inhibition of mTOR pathway and targeting RBM33 may be a promising strategy for HNSC treatment.

2023-09-05 | GSE242281 | GEO

RBM33 Acts as an m6A Reader Essential for ALKBH5-mediated m6A Demethylation and Head and Neck Squamous Carcinoma Tumorigenesis [PAR-CLIP]

2023-09-05 | GSE242283 | GEO

RBM33 Acts as an m6A Reader Essential for ALKBH5-mediated m6A Demethylation and Head and Neck Squamous Carcinoma Tumorigenesis [m6A-seq]

2023-09-05 | GSE242276 | GEO