METTL14 is a chromatin regulator independent of its RNA N6-methyladenosine methyltransferase activity

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.

Analysis of CIP2 A expression and prognosis in non-small cell lung cancer patients / 中国生化药物杂志

Objective To study the different expressions of cancerous inhibitor of protein phosphatase 2A (CIP2A)in non-small cell lung cancer (NSCLC),investigate its clinical significance and potential prognostic value.Methods Immunohistochemical and real-time polymerase chain reaction (PCR)were used to detect the expressions of CIP2A mRNA and protein in two groups of sixty paired NSCLC specimens and adjacent non-cancer tissues.The relationship between its expression and clinical pathological data and prognostic factors were analysed. Results The expression of CIP2A mRNA in NSCLC specimens was higher than those in adjacent non-cancer tissues(P<0.01 );The expression of CIP2A protein in NSCLC tissues was significantly higher than that in the corresponding adjacent non-cancer tissues (P<0.01 ).The expression of CIP2A was closely correlated with the differentiation and lymph node metastasis of NSCLC tissues (P<0.05 ),while incorrelated with sex,age,pathematology type,tumor size and tumor node metastasis (TNM)stage.Conclusion CIP2A highly expresses in NSCLC,and the expression of CIP2A will increase with the differentiation and lymph node metastasis of NSCLC tissues.The expression of CIP2A and lymph node metastasis can be used as an independent risk factor for the prognosis of patients with NSCLC.