Dataset Information

Loss of m⁶A Methyltransferase METTL5 Promotes Cardiac Hypertrophy Through Epitranscriptomic Control of SUZ12 Expression.

ABSTRACT: Enhancement of protein synthesis from mRNA translation is one of the key steps supporting cardiomyocyte hypertrophy during cardiac remodeling. The methyltransferase-like5 (METTL5), which catalyzes m⁶A modification of 18S rRNA at position A₁₈₃₂, has been shown to regulate the efficiency of mRNA translation during the differentiation of ES cells and the growth of cancer cells. It remains unknown whether and how METTL5 regulates cardiac hypertrophy. In this study, we have generated a mouse model, METTL5-cKO, with cardiac-specific depletion of METTL5 in vivo. Loss function of METTL5 promotes pressure overload-induced cardiomyocyte hypertrophy and adverse remodeling. The regulatory function of METTL5 in hypertrophic growth of cardiomyocytes was further confirmed with both gain- and loss-of-function approaches in primary cardiomyocytes. Mechanically, METTL5 can modulate the mRNA translation of SUZ12, a core component of PRC2 complex, and further regulate the transcriptomic shift during cardiac hypertrophy. Altogether, our study may uncover an important translational regulator of cardiac hypertrophy through m6A modification.

SUBMITTER: Han Y

PROVIDER: S-EPMC8920042 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Loss of m6A Methyltransferase METTL5 Promotes Cardiac Hypertrophy Through Epitranscriptomic Control of SUZ12 Expression.

Han Yanchuang Y Du Tailai T Guo Siyao S Wang Lu L Dai Gang G Long Tianxin T Xu Ting T Zhuang Xiaodong X Liu Chen C Li Shujuan S Zhang Dihua D Liao Xinxue X Dong Yugang Y Lui Kathy O KO Tan Xu X Lin Shuibin S Chen Yili Y Huang Zhan-Peng ZP

Frontiers in cardiovascular medicine 20220228

Enhancement of protein synthesis from mRNA translation is one of the key steps supporting cardiomyocyte hypertrophy during cardiac remodeling. The methyltransferase-like5 (METTL5), which catalyzes m6A modification of 18S rRNA at position A1832, has been shown to regulate the efficiency of mRNA translation during the differentiation of ES cells and the growth of cancer cells. It remains unknown whether and how METTL5 regulates cardiac hypertrophy. In this study, we have gene ...[more]

PMID: 35295259

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Project description:BackgroundRibosomal RNA N6-methyltransferase METTL5 was reported to catalyze m6A in 18S rRNA. We aimed to investigate the expression and prognostic features of METTL5 in gastric cancer (GC).MethodsIn this study, 168 GC patients and their corresponding adjacent tissues were collected. Immunohistochemical staining was used to detect the expression of METTL5 protein. Univariate and multivariate Cox analysis were used to dertermine the prognostic role of METTL5 protein in GC, and a nomogram was constructed to evaluate GC patients' prognosis based on METTL5 expression. Data from TCGA and GEO database were also used to validate the prognostic value of METTL5 in GC patients on mRNA level. We further performed GSEA enrichment analysis to explore the possible function and related pathways related to METTL5.ResultsMETTL5 protein in gastric cancer tissues (GCTs) was significantly decreased compared with adjacent normal tissues (ANTs) and adjacent intestinal metaplasia tissues (AIMTs) (P < 0.001, respectively). Meanwhile, METTL5 expression was negatively correlated with clinicopathologic stage. According to multivariate Cox proportional hazards model analysis, METTL5 protein expression was a good independent predictor of GC prognosis (p < 0.05). Patients with high METTL5 expression had better prognosis. The nomogram constructed based on METTL5 expression could predict the prognosis of GC patients well. GSEA analysis showed that genes of METTL5 low expression group were enriched in some oncogenic signaling pathways such as ERBB, MAPK, JAK-STAT, Wnt, and mTOR, as well as some immune pathways, including Fc-gamma R mediated phagocytosis, Fc-epsilon Ri, chemokine, T cell receptor and B cell receptor signaling pathway. While the high expression group of METTL5 was mainly related to oxidative phosphorylation, nucleotide excision repair and mismatch repair.ConclusionsMETTL5 protein was decreased in GCTs compared with AIMTs and ANTs, and it may be a potential prognostic biomarker in GC.

Dataset Information

Loss of m⁶A Methyltransferase METTL5 Promotes Cardiac Hypertrophy Through Epitranscriptomic Control of SUZ12 Expression.

Publications

Loss of m<sup>6</sup>A Methyltransferase METTL5 Promotes Cardiac Hypertrophy Through Epitranscriptomic Control of SUZ12 Expression.

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