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Table 1 The biological functions of m6A

From: Advances in the role of m6A RNA modification in cancer metabolic reprogramming

Functions Regulators Underlying mechanism References
RNA maturation METTL3, METTL14, WTAP METTL3, METTL14, and WTAP all localize with pre-mRNA processing factors residing in the nuclear speckles [116]
  FTO The cellular FTO protein is present in a dot-like manner in nucleoplasm, and partially colocalizes with splicing or splicing-related speckle factors [18]
  ALKBH5 ALKBH5 colocalizes well with mRNA-processing factors in nuclear speckles. SRPK1 translocate from nucleic locations to dot-like cytoplasmic sites, and ASF/SF2 switches from splicing factors to export adaptor proteins, promoting mRNA export, when depleting ALKBH5 [50]
  FTO m6A was overrepresented in both alternative cassette exons and intron retention splicing events and peaks within cassette exons increased upon FTO depletion [49]
  YTHDC1 YTHDC1 promotes exon inclusion of targeted mRNAs through facilitating SRSF3 while blocking SRSF10 mRNA binding [53]
  HNRNPA2B1 HNRNPA2B1 binds to m6A containing sites on nuclear pri-miRNAs, and it interacts with the DGCR8 protein to facilitate the processing and maturation of pri-miRNAs [42]
  HNRNPC An m6A site in the lncRNA MALAT1 induces a local change in structure that increases the accessibility of a U5-tract for recognition and binding by HNRNPC [46, 57]
RNA degradation YTHDF2 YTHDF2 selectively binds to and destabilizes m6A-containing mRNA through direct recruitment of the CCR4-NOT deadenylase complex [62]
  YTHDF2 P/Q/N-rich N terminus of YTHDF2 localizes the YTHDF2-m6A-mRNA complex to P bodies for committed degradation [63]
  HuR HuR interacted with SOX2 mRNA containing m6A to block the miRNA-dependent mRNA degradation and increase the stability [66]
RNA translation METTL3 mRNA nuclear export diminished when silencing METTL3 [68]
  ALKBH5 mRNA nuclear export accelerated when knocking down ALKBH5 [50]
  FMRP FMRP promoted the nuclear export of methylated mRNAs in a CRM1-dependent way during neural differentiation [69]
  YTHDF1 YTHDF1-mediated translation promotion increases translation efficiency, ensuring effective protein production from dynamic transcripts that are marked by m6A [70]
   The presence of an m6A within a codon alters cognate tRNA selection to be kinetically unfavorable, with m6A acting as a barrier to tRNA accommodation and translation elongation [71]
  ZCCHC4 ZCCHC4, a new m6A methyltransferase, catalyzed m6A4220 methylation in human 28S rRNA and also interacted with a subset of mRNAs, to affected global translation [73, 74]