Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE224890 | GEO | 2023/10/05
REPOSITORIES: GEO
Similar Datasets
Project description:Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer
| PRJNA932911 | ENA
Project description: Not available
| S-EPMC10589265 | biostudies-literature
Project description:Allergic asthma is a common disease. We aimed to investigate the role of METTL16, an N6-methyladenosine (m6A) writer, in allergic asthma and epithelial homeostasis. Here we show that pulmonary METTL16 expression was decreased in patients with allergic asthma and in a murine model of allergic asthma, particularly in airway epithelial cells. Genetic depletion of Mettl16 enhanced type 2 cytokine production and exacerbated epithelial-to-mesenchymal transition (EMT), whereas lung-specific METTL16 overexpression attenuated allergic airway inflammation and remodeling. Mechanistically, METTL16 promoted epithelial arginine biosynthesis and thereby suppressed IL-1β production. Furthermore, loss of Mettl16 impaired m6A modification of Ass1 mRNA, and increased Ass1 expression was associated with arginine biosynthesis. Our findings identify METTL16 as a critical regulator of allergic asthma and suggest it as a potential therapeutic target.
2026-08-04 | GSE341970 | GEO
Project description:METTL16 belongs to methyltransferase like (METTL) family and could install m6A marks on its substrates. Here, we uncover a tumor-promoting role of METTL16 in AML and LSC self-renewal. To explore the mechanism underlying the oncogenic function of METTL16 in AML, we performed m6A-seq and RNA-seq. Via integrated analysis of m6A-seq data and RNA-seq data, we identified two bona fide targets of METTL16, BCAT1 and BCAT2. METTL16 functions as an m6A methyltransferase to regulate expression of BCAT1 and BCAT2, which contribute to reprogramming of BCAA metabolism.
2023-01-12 | GSE189995 | GEO
Project description:Maintenance of the intracellular levels of the methyl donor S-adenosylmethionine (SAM) is essential for a wide variety of biological processes. We demonstrate that the N6-adenosine methyltransferase METTL16 regulates expression of MAT2A, which encodes the only SAM synthetase expressed in most cells. Upon SAM depletion by methionine starvation, cells induce MAT2A expression by enhanced splicing of a retained intron. Induction requires METTL16 and its methylation substrate, a vertebrate conserved hairpin (hp1) in the MAT2A 3´ UTR. Increasing METTL16 occupancy on the MAT2A 3´ UTR is sufficient to induce efficient splicing. We propose that under SAM-limiting conditions, METTL16 occupancy on hp1 increases due to inefficient enzymatic turnover, which in turn promotes MAT2A splicing. Interestingly, human and S. pombe METTL16 methylate the U6 spliceosomal snRNA at a sequence identical to hp1. These observations suggest that the conserved U6 snRNA methyltransferase evolved an additional function in vertebrates to regulate SAM homeostasis.
2017-05-18 | GSE90914 | GEO
Project description:The RNA N6-methyladenosine (m6A) modification has emerged as an essential regulator of vertebrate embryogenesis and malignancies. However, its functions and underlying molecular mechanisms in the expansion of hematopoietic stem and progenitor cells (HSPCs) during early embryonic development remain elusive. Here we show that Mettl16, an RNA methyltransferase identified recently, is specifically required for HSPC expansion during zebrafish early embryonic development in an m6A-dependent manner. In mettl16 deficient embryos, HSPCs exhibit defective proliferation capacity due to G0/G1 arrest. Mechanistically, HSPC proliferation is blocked by impaired methyltransferase function of Mettl16 in vivo. We identify cell cycle gene mybl2b as a novel direct m6A target of Mettl16, and Mettl16 deficiency destabilizes mybl2b mRNA, which is mediated by m6A reader Igf2bp1. Moreover, we revealed that the METTL16-m6A-MYBL2-IGF2BP1 signaling axis in G1/S progression is conserved in humans. Collectively, our findings demonstrate the critical function of m6A modification deposited by Mettl16 in HSPC expansion during early embryonic development.
2024-03-04 | GSE225136 | GEO
Project description:METTL16 belong to methyltransferase like (METTL) family and possesses the ability to deposit N6-methyladenosine (m6A) in mRNA. We have conducted m6A-seq with poly(A) RNAs isolated from the whole HEK293T cells upon METTL16 knockdown to identify the transcripts with hypo m6A peaks after METTL16 knockdown, and also conducted RIP-seq with HEK293T cells to determine the METTL16-bound transcripts. However, we found that the transcripts with hypo m6A peaks upon METTL16 knockdown only account for a small proportion of METTL16-bound transcripts. We suppose one of the possibility reasons might be due to spatiotemporal installation of m6A. To support our hypothesis, we performed additional m6A seq with nascent RNA and nuclear poly(A) RNA isolated from HEK293T cells with METTL16 knockdown.
2021-10-28 | GSE156795 | GEO
Project description:N6-methyladenosine (m6A) is one of the most prevalent RNA modifications in eukaryotes. The METTL16 enzyme catalyzes the m6A modification at position 43 of U6 snRNA, which is very important for the 5'-splice site recognition by U6 during pre-mRNA splicing. Loss of METTL16 results in the death of mouse early embryos, making it difficult to study the function of METTL16 in development. Here we characterize METTL16 in the context of Drosophila melanogaster development. We showed that dMETTL16 localizes in nuclei of all endoreduplicating cells, such as cells in salivary glands, with a pattern coinciding with the replication timing. In addition, dMETTL16 is present in diploid cells of the gonad, suggesting that it plays a role in gonadal development. To further determine the function of dMETTL16, we used the CRISPR/Cas9 system to construct dMETTL16 mutations and discovered that mutants are semilethal at the larval stage while surviving adults are female sterile. More interestingly, a 50% reduction of U6 gene dosage leads to complete lethality of dMETTL16 mutants at the larval stage suggesting that loss of U6 function is one of the primary defects in the mutants. Using a novel antibody-based in vitro methylation assay, we proved that U6 is a substrate of dMETTL16. To determine whether the phenotypes depend on m6A methylase activity, we constructed point mutations of the active site of dMETTL16, and discovered that ovarian development was restored while maternal lethality ensures. These results suggest that dMETTL16 has important functions that are independent of its methyltransferase activity. Our study establishes Drosophila as a genetically tractable model for the study of dMETTL16’s function and can be explored to uncover additional dMETTL16 m6A targets.
2026-07-05 | GSE271111 | GEO
Project description:METTL16 belongs to methyltransferase like (METTL) family and could install m6A marks on its substrates. Here, we uncover a tumor-promoting role of METTL16 in AML and LSC self-renewal. To explore the mechanism underlying the oncogenic function of METTL16 in AML, we performed m6A-seq and RNA-seq. Via integrated analysis of m6A-seq data and RNA-seq data, we identified two bona fide targets of METTL16, BCAT1 and BCAT2. METTL16 functions as an m6A methyltransferase to regulate expression of BCAT1 and BCAT2, which contribute to reprogramming BCAA metabolism.
2023-01-12 | GSE190044 | GEO
Project description:In this study, we generated viable mettl16 knockout Drosophila and GFP knock-in Drosophila via the CRISPR/Cas9 technique, which provides an excellent in vivo model for investigating the precise functions of the Mettl16 protein. Subsequent staining assays revealed that Drosophila Mettl16 is a ubiquitously expressed nuclear protein, and its depletion does not affect the translational level in flies. Loss of Mettl16 results in multiple developmental phenotypes, including developmental delay, reduced locomotor activity, flightlessness, and sterility. Through MeRIP-seq and splicing analyses, we found that Mettl16 mediates m6A methylation of only a small subset of mRNAs. The reduced m6A modification level on its conserved methylation substrate U6 snRNA induces significant global changes in splicing events
2026-07-17 | GSE324097 | GEO