Dataset Information

N6-methyladenosine RNA modification regulates cotton drought response in a Ca²⁺ and ABA-dependent manner.

ABSTRACT: N⁶ -methyladenosine (m⁶ A) is the most prevalent internal modification present in mRNAs, and is considered to participate in a range of developmental and biological processes. Drought response is highly regulated at the genomic, transcriptional and post-transcriptional levels. However, the biological function and regulatory mechanism of m⁶ A modification in the drought stress response is still poorly understood. We generated a transcriptome-wide m⁶ A map using drought-resistant and drought-sensitive varieties of cotton under different water deficient conditions to uncover patterns of m⁶ A methylation in cotton response to drought stress. The results reveal that m⁶ A represents a common modification and exhibit dramatic changes in distribution during drought stress. More 5'UTR m⁶ A was deposited in the drought-resistant variety and was associated with a positive effect on drought resistance by regulating mRNA abundance. Interestingly, we observed that increased m⁶ A abundance was associated with increased mRNA abundance under drought, contributing to drought resistance, and vice versa. The demethylase GhALKBH10B was found to decrease m⁶ A levels, facilitating the mRNA decay of ABA signal-related genes (GhZEP, GhNCED4 and GhPP2CA) and Ca²⁺ signal-related genes (GhECA1, GhCNGC4, GhANN1 and GhCML13), and mutation of GhALKBH10B enhanced drought resistance at seedling stage in cotton. Virus-induced gene silencing (VIGS) of two Ca²⁺ -related genes, GhECA1 and GhCNGC4, reduced drought resistance with the decreased m⁶ A enrichment on silenced genes in cotton. Collectively, we reveal a novel mechanism of post-transcriptional modification involved in affecting drought response in cotton, by mediating m⁶ A methylation on targeted transcripts in the ABA and Ca²⁺ signalling transduction pathways.

SUBMITTER: Li B

PROVIDER: S-EPMC10214760 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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N6-methyladenosine RNA modification regulates cotton drought response in a Ca2+ and ABA-dependent manner.

Li Baoqi B Zhang Mengmeng M Sun Weinan W Yue Dandan D Ma Yizan Y Zhang Boyang B Duan Lingfeng L Wang Maojun M Lindsey Keith K Nie Xinhui X Zhang Xianlong X Yang Xiyan X

Plant biotechnology journal 20230322 6

N6 -methyladenosine (m6 A) is the most prevalent internal modification present in mRNAs, and is considered to participate in a range of developmental and biological processes. Drought response is highly regulated at the genomic, transcriptional and post-transcriptional levels. However, the biological function and regulatory mechanism of m6 A modification in the drought stress response is still poorly understood. We generated a transcriptome-wide m6 A m ...[more]

PMID: 36949572

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Project description:BackgroundN6-methyladenosine (m6A) is associated with mammalian mRNA biogenesis, decay, translation and metabolism, and also contributes greatly to gastrointestinal tumor formation and development. Therefore, the specific mechanisms and signaling pathways mediated by methyltransferase-like 3 (METTL3), which catalyzes the formation of m6A chemical labeling in stomach adenocarcinoma (STAD), are still worth exploring.MethodsQuantitative real-time PCR (qRT-PCR) was constructed to detect the expression of METTL3 in gastric cancer cell lines and patient tissues. The biological function of METTL3 was investigated in vitro/in vivo by Cell Counting Kit-8, colony formation assay, Transwell assay and nude mouse tumorigenesis assay. Based on the LinkedOmics database, the genes co-expressed with METTL3 in the TCGA STAD cohort were analyzed to clarify the downstream targets of METTL3. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA stability analysis were employed to explore the mechanism of METTL3 in gastric cancer progression.ResultsWe analyzed TCGA data and found that METTL3 was frequently elevated in STAD, and demonstrated that METTL3 was present at high levels in clinical STAD tissues and cells. High METTL3 expression was more likely to have advanced TNM tumors and distant metastasis. On the other hand, METTL3 silencing effectively impeded the higher oncogenic capacity of AGS and HGC27 cells in vivo and in vitro, as reflected by slowed cell growth and diminished migration and invasion capacities. Continued mining of the TCGA dataset identified the co-expression of angiopoietin-like 3 (ANGPTL3) and METTL3 in STAD. Lower level of ANGPTL3 was related to increased level of METTL3 in STAD samples and shorter survival times in STAD patients. ANGPTL3 enrichment limited the growth and metastasis of STAD cells. Besides, ANGPTL3 mRNA levels could be decreased by METTL3-dominated m6A modifications, a result derived from a combination of MeRIP-qPCR and RNA half-life experiments. Importantly, the inhibitory effect of METTL3 silencing on cancer could be reversed to some extent by ANGPTL3 inhibition.ConclusionsOverall, our findings suggested that METTL3 functioned an oncogenic role in STAD by reducing ANGPTL3 expression in an m6A-dependent manner. The discovery of the METTL3-ANGPTL3 axis and its effect on STAD tumor growth will contribute to further studies on the mechanisms of gastric adenocarcinoma development.

Dataset Information

N6-methyladenosine RNA modification regulates cotton drought response in a Ca²⁺ and ABA-dependent manner.

Publications

N6-methyladenosine RNA modification regulates cotton drought response in a Ca<sup>2+</sup> and ABA-dependent manner.

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