Fig 2: METTL14 negatively regulates antiviral response to RNA virus in vivo. A) Survival of Mettl14 +/+ and Mettl14 +/− mice infected intravenously with VSV (1 × 108 PFU per mouse). B) Hematoxylin‐and‐eosin‐stained images of lung sections of Mettl14 +/+ and Mettl14 +/− mice infected by intraperitoneal injection of VSV (1 × 108 PFU per mouse) for 48 h, Scale bars, 100 µm. C) ELISA analysis of IFN‐β of Serum from Mettl14 +/+ and Mettl14 +/− mice infected by intraperitoneal injection of VSV (1 × 108 PFU per mouse) for 8 h. D) qPCR analysis of Ifnb1 mRNA (middle right) of the spleen (left), liver (middle), and lungs (right) from Mettl14 +/+ and Mettl14 +/− (six per group) mice infected by intraperitoneal injection of VSV (1 × 108 PFU per mouse) for 48 h. E) qPCR analysis of VSV RNA of the spleen (left), liver (middle), and lungs (right) from Mettl14 +/+ and Mettl14 +/− mice infected by intraperitoneal injection of VSV (1 × 108 PFU per mouse) for 48 h. F) Plaque assay of VSV titers of the spleen, liver, and lungs from Mettl14 +/+ and Mettl14 +/− mice infected by intraperitoneal injection of VSV (1 × 108 PFU per mouse) for 48 h. Each symbol represents an individual mouse; small horizontal lines indicate the mean. Data information: Data are presented as mean ± S.D. Log‐rank test (A); Two‐tailed unpaired Student's t‐test; *P < 0.05; **P < 0.01 (C–F).

Fig 3: Correlation between m6A regulators with clinical outcomes in nasopharyngeal carcinoma. (a) Immunohistochemistry of m6A writer METTL3, WTAP, and hematoxylin and eosin (H&E) staining in NPE tissues. (b) Immunohistochemistry of m6A writer METTL3, WTAP, and H&E staining in primary NPC and paired recurrent NPC tissues. (c) K-M curve of overall survival in patients with different METTL3 and WTAP expression. (d) Correlation between expression of m6A regulators including eraser reader and writers in head and neck cancer patients’ tissues in TCGA-HNSC cohort. (e) The scheme of the role of m6A and regulators in the occurrence and recurrence of nasopharyngeal carcinoma. METTL3: methyltransferase 3; METTL14: methyltransferase 14; WTAP: WT1 associated protein; NPE: normal nasopharyngeal epithelium; pNPC: primary nasopharyngeal carcinoma; rNPC: recurrent nasopharyngeal carcinoma; m6A: N6-methyladenosine; TCGA: The Cancer Genome Atlas; HNSC: head and neck squamous cell carcinoma.

Fig 4: METTL14 overexpression suppresses cell invasion and migration ability of U2OS and 143B cells. (A and B) Wound-healing assay was used to detect the effects of METTL14 forced expression in cell migration ability of U2OS (A) and 143B cells (B). The representative images were taken at 0 h, 24 h and 48 h respectively after transfection (Bar: 200 μm, n = 9). (C and D) Transwell assays showing the changes of invasion ability with METTL14 overexpression in U2OS (C) and 143B cells (D) (Bar: 150 μm, n = 7). Bar graph representing the quantification of invasive cells. Data are expressed as mean ± SEM. ***P < 0.001.

Fig 5: The dynamic m6A epitranscriptomic landscape in DPSC differentiation. A DPSCs were induced with osteo/odontogenic medium for 0, 7, and 14 days, and then the total m6A level in the RNA polls was quantified by the colorimetric method. B The m6A methylation landscape in the genome-wide transcriptome was evaluated by m6A RIP-seq. Distribution of m6A peaks in the 3′ UTR, CDS region and 5′ UTR. C Pie chart analysis of the m6A peak fraction in transcript segments. D Specific and conserved motif sequences of high-confidence m6A peaks identified by the HOMER database. E Epitranscriptome profile of m6A-tagged mRNAs in DPSCs after odontogenic differentiation. F Gene Ontology enrichment analysis of differentially m6A methylated and expressed transcripts. G The concentrations of SAM, SAH and potential of m6A establishment were qualified by LC‒MS/MS. Metabolites with a VIP value > 1 were further subjected to statistical analysis (n = 6). H The mRNA expression of METTL3, METTL14, and WTAP during DPSC mineralization, as evaluated by qPCR (n = 3). I The protein expression of METTL3, METTL14, and WTAP in DPSCs was evaluated by western blotting. SAM: S-adenosylmethionine; SAH: S-adenosylhomocysteine. Significance was determined via ANOVA or Student’s t test. The quantitative data are presented as the mean ± SD *p < 0.05. **p < 0.01. ***p < 0.001