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The impact of small molecule L-2-hydroxyglutarate on mRNA m6A in renal cancer

ABSTRACT: To investigate L-2HG's impact on RNA methylation (m6A), we performed a comparitive analysis of m6A IP profiles in high L-2HG RCC cells compared with low L-2HG Cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228081 | GEO | 2025/11/11

REPOSITORIES: GEO

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Biologic roles of mRNA N6-methyladenosine (m6A) in high L-2-hydroxyglutarate renal cancer

Project description:The oncometabolite L-2-hydroxyglutarate (L-2HG) is commonly elevated in the most prevalent form of renal cancer. Oncometabolites can alter the epigenome by disrupting the activities of enzymes that mediate both DNA and histone demethylation. L-2HG has also been shown to inhibit the enzymatic activity of the RNA demethylases ALKBH5 and FTO. Both enzymes demethylate the N6-methyladenosine (m6A) mark, the most prevalent RNA modification within mRNA. We performed an integrative analysis on the role of m6A in high L-2HG renal carcinoma. On a global level, L-2HG-induced m6A promotes reduced transcript levels consistent with the well-established role of m6A in reducing mRNA stability. Ablation of METTL3, a key component of the m6A methyltransferase complex, led to bimodal effects on the transcriptome. METTL3 activity promoted expression of genes related to interferon signalling. In contrast, METTL3 suppressed the expression of genes related to cell cycle, specifically the G2-M phase, with concomitant effects on proliferation and cell cycle progression. Furthermore, m6A is associated with splicing events including retained introns, not previously implicated in tumor cells. Our data provide new insights into the functional role of m6A in renal cancer which have implications for both intrinsic tumor cell biology and the immune response.

2025-11-18 | GSE310263 | GEO

The impact of small molecule L-2-hydroxyglutarate on mRNA m6A in renal cancer

Project description:The impact of small molecule L-2-hydroxyglutarate on mRNA m6A in renal cancer

| PRJNA948016 | ENA

The anti-leukemic effect of R-2HG depends on its acting as an m6A mRNA modifier-M6A Seq

Project description:m6A-seq in NOMO-1, MA9.3RAS and MA9.3ITD cells with or without R-2HG treatment.

2017-12-14 | GSE87190 | GEO

TMT spectrometry unveils key M6a interactorsTMT spectrometry unveils key M6a interactors

Project description:The membrane glycoprotein M6a -together with proteolipid protein (PLP), DM20 and M6b- belongs to the tetraspan PLP family. M6a is a neuronal surface protein that promotes neuronal stem cell differentiation, migration, neurite and axonal outgrowth, filopodia/spine induction and synapse formation in primary neuronal cultures and non-neuronal cell lines. M6a has two extracellular loops (EC1 and EC2), four transmembrane domains, one intracellular loop and the N and C terminus facing the cell cytoplasm. However, the complete mechanism of action or proteins associated with it through its extracellular loops remained unknown. In previous work we provided strong evidence that M6aÃƒâ€šÃ‚Â´s extracellular loops widely contribute to its function. To asses this question, we designed and purified a chimera protein (M6a-loops as a bait protein) which was subjected to co-immunoprecipitation (Co-Ip) with rat hippocampi homogenates followed by TMT-MS. The TMT-MS and data analysis was done by the Proteomics Core Facility from the European Molecular Biology Laboratory (EMBL, Heidelberg, Germany).

2020-06-29 | PXD017347 | Pride

M6A reduction relieves FUS-associated ALS granules [m6A-IP]

Project description:M6A reduction relieves FUS-associated ALS granules [m6A-IP]

| PRJNA1014475 | ENA

The two enantiomers of 2-hydroxyglutarate differentially regulate cytotoxic T cell function

Project description:2-hydroxyglutarate (2HG) is a by-product of the TCA cycle, and is readily detected in the tissues of healthy individuals. 2HG is found in two enantiomeric forms: S-2HG and R-2HG. Here, we investigate the differential roles of these two enantiomers in CD8+ T cell biology, where we found they had highly divergent effects on proliferation, differentiation, and T cell function. We show here an analysis of structural determinants that likely underlie these differential effects on specific a-ketoglutarate (aKG)-dependent enzymes. Treatment of CD8+ T cells with exogenous S-2HG, but not R-2HG, increased CD8+ T cell fitness in vivo, and enhanced anti-tumour activity. These data show that S-2HG and R-2HG should be considered as two distinct and important actors in the regulation of T cell function.

2023-07-21 | GSE212738 | GEO

m6A RNA Methylation is Critical for Adequate Exit from NaM-CM-/ve Pluripotency and Execution of Mammalian Development (m6a-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. m6A-seq was measured from total RNA in mouse embryonic stem cells (ESCs), embroid bodies (EBs) and embronic fibroblasts (MEF). 3 biological replicates are available from BVSC ESC line and EBs, and two biological replicates are available for MEFs. Each sample consist of IP to m6A and control input

2014-11-02 | E-GEOD-61995 | biostudies-arrayexpress

Effect of L-2-hydroxyglutarate on gene expression in mice round spermatids

Project description:2-hydroxyglutarate (2HG) is known to function as an epigenetic regulator in cancer and certain transient biological processes. Among all organs in mice, the testis contains the highest baseline physiological levels of 2HG. We found that L-2HG is generated in specific stages of spermatogenesis namely starting from pachytene up to round spermatids.

2025-05-21 | GSE238241 | GEO

The impact of small molecule L-2-hydroxyglutarate

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-11-17 | GSE228082 | GEO

Activin/Nodal-dependent N6-methyladenosine (m6A) deposition in human pluripotent stem cells

Project description:This experiment was designed to probe the function of Activin/Nodal signalling in the deposition of m6A in human pluripotent stem cells (hPSCs). hPSCs were cultured in presence of Activin or subjected to short-term inhibition of Activin/Nodal signalling for 2h using the receptor antagonist SB-431542 (IP). The global abundance of m6A was then measured by nuclear-enriched methylated RNA immunoprecipitation followed by deep sequencing (NeMeRIP-seq). Pre-NeMeRIP input RNA was used as control to normalise for the changes in gene expression in the two conditions.

2017-12-26 | E-MTAB-5229 | biostudies-arrayexpress

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