Fig. 1: RBFOX2 recognizes m6A on paRNA.
a, Top: a protein–protein interaction network with the top-ranked (n = 50) m6A-associated proteins on caRNAs in K562 cells. Bottom: Venn diagram of top-ranked (n = 20) m6A-associated proteins on caRNAs between K562 and HepG2 cells. The highlighted protein (dotted circle) is shared between K562 and HepG2 cells. b, Average profile (top) and heat map (bottom) showing RBFOX2 binding intensity at m6A peak centres and the flanking 2.5 kb regions in K562 cells. rep, replicate. c, Average profile of RBFOX2 binding intensity at RBFOX2 peak centres and the flanking 2.5 kb regions in K562 cells. RBFOX2 peaks29,30 were categorized into two groups according to whether they overlapped with m6A (m6A) or not (non-m6A). d, LC–MS/MS showing m6A enrichment in RBFOX2-bound RNA while depleted in the FT portion (n = 6, three technical replicates over two biological replicates). Data are represented as mean values ± standard deviation. Two-sided P value was calculated by Student’s t-test. e, Distribution of m6A or RBFOX2 peaks29,30 at distinct genomic regions including promoter, exonic, intronic, transcription termination sites (TTS) and intergenic regions annotated by HOMER48 in K562 cells. ‘(+)’ sign represents regions harbouring m6A (+) or bound by RBFOX2 (+), while the sign ‘(−)’ indicates the absence of m6A (−) or RBFOX2 (−). f, Top consensus sequences on RBFOX2-bound sites that were marked with m6A (caRNA m6A-SAC-seq) using HOMER48 motif discovery algorithm. g, Oligo pulldown assay showing RBFOX2 (top) and RRM domain of RBFOX2 (bottom) bound an m6A-containing RNA probe with higher affinity than the unmethylated control.
