Fig. 2: IGF2BP3 regulates serine biosynthesis as an m⁶A reader.

A Bubble diagram showing the enrichment of metabolic pathways by the C¹³-labeled metabolites with reduced levels after IGF2BP3 KD in Molm13 cells. B Heatmaps showing levels of representative C¹³-labeled metabolites after IGF2BP3 KD in Molm13 cells. C The total levels and isotopolog distribution (M + n, n refers to numbers of ¹³C) of purines measured by LC-MS in Molm13 cells transduced with IGF2BP3 shRNAs or shNS and grown in medium containing U-[¹³C]-glucose. D Schematic of the serine synthesis pathway and its downstream pathways. E The levels of C¹³-labeled serine (M + 3) were measured by LC-MS in Molm13 cells transduced with IGF2BP3 shRNAs or shNS and grown in medium containing U-[¹³C]-glucose. F–H Intracellular serine level measured by fluorescence-based serine detection assays in Molm13 cells transduced with shRNAs (F) or sgRNAs (G) targeting IGF2BP3 or shRNAs targeting METTL14 (H), compared to those with negative control (shNS). I The Venn diagram showing the overlap of significantly downregulated genes (adjusted P < 0.05, fold change <0.67) in Molm13 cells with IGF2BP3 KD, as well as in U937 BP3-mAID cells treated with 5’Ph-IAA for 6 or 24 h to induce degradation of the IGF2BP3 protein. J Pie chart showing numbers of transcripts with or without m⁶A modifications among the 61 overlapping genes in (H), and heatmap showing expression changes of the 48 m⁶A-containing transcripts in IGF2BP3 KD Molm13 cells or IGF2BP3-depleted U937 cells. K GO enrichment analysis of the 48 candidate targets of IGF2BP3 in (I). The degrees of interactions were generated by STRING. Mean ± SD values are shown. n = 2 biologically independent repeats in (C) and (E), while n = 3 biologically independent repeats in (F–H). P-values were calculated with one-sided Hypergeometric test (A, K); two-tailed Wald test adjusted with Benjamini-Hochberg Procedure (I); two-tailed student’s t-test (F–H); Source data are provided as a Source Data file.