Fig. 1: METTL1 may regulate TP53 abundance through its 3’UTR m⁷G methylation in cancer cells.

a, b Kaplan-Meier survival analysis in TCGA database for Glioma (TCGA-GBMLGG): the entire dataset (a), and cases with mutant TP53 (b). The patients were divided into two groups of equal size based on the METTL1 levels. The ones lower than the median value are all grouped into the “Low” group while the ones higher than the median value are all grouped into “High”. P-value detected by log-rank test. c Gene Set Enrichment Analysis (GSEA) of genes in ‘cell cycle’ and ‘p53 signaling pathway’ KEGG pathways against ranked list of genes according to METTL1 expression level. d The correlation of CERES dependency score between METTL1 and WDR4, with standard error marked in gray. The CERES was developed to estimate gene-dependency level from CRISPR-Cas9 essentiality screens while accounting for the effects⁸⁰. e The integrative genomics viewer (IGV) plots showing the m⁷G-MeRIP-seq peaks at the 3’ UTR end of TP53, which also overlap with METTL1 and WDR4 PAR-CLIP peaks. A minor m⁶A peak was detected in the distant CDS region adjacent to 5’UTR region. Y-axis showing counts per ten million reads. f IGV plots showing the m⁷G-MeRIP-seq peaks at the 3’ UTR end of TP53 upon stable knockdown of METTL1 compared to control in HepG2 (GSE112276). Y-axis showing counts per ten million reads. g Relative m⁷G methylation levels of the TP53 3’ UTR locus upon METTL1 knockdown in HepG2 cells, normalized to the methylation level in the knockdown control cells. Mean ± SEM (n = 3) with two-tailed Student’s t-tests. h Relative m⁶A (gray) and m⁷G (blue) methylation levels of the 3’ UTR region of TP53 based on MeRIP enrichment followed by qPCR quantification. Mean ± SEM of three independent experiments. i The mRNA levels of TP53 in different cell lines. For each cell, the TP53 expression level was normalized to total RNA amount respectively. And the comparison across the cell lines were normalized to U87MG. Mean ± SEM of three independent experiments. j Spearman correlation of the 3’ UTR m⁷G methylation level and the mRNA abundance of TP53. Significance was determined by two-sided Pearson’s correlation test. All source data are provided as a Source Data file.