Table 1 The biological functions of m⁶A

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]