Fig. 1
From: The m6A epitranscriptome on neural development and degeneration
m6A-associated proteins and molecular pathways. N6-methyladenosine (m6A) modifications have important roles in a series of RNA-centric regulatory mechanisms. The illustration depicts the roles of m6A “writer”, “eraser” and “reader” complexes in regulating mRNAs. m6A biogenesis in mammalian cells (nucleus) is catalysed by a core methyltransferase complex comprising METTL3, METTL14 and WTAP, and it can be reversed by m6A demethylases (FTO or ALKBH5). METTL5 and METTL16 have recently been reported as additional writers to catalyze the addition of m6A on the 3′UTR of 18S rRNA and U6 snRNA, respectively. m6A can be recognized by reader proteins in both the nucleus and cytoplasm. For example, YTHDF2/3 can participate in post-transcriptional regulation by recruiting different complexes to m6A sites. m6A-modification of mRNAs can impact RNA nuclear splicing, export, stability, trafficking, and translation efficiency. METTL, methyltransferase-like; WTAP, WT1-associated protein; RBM15, RNA-binding motif protein 15 or its paralog RBM15B; VIRMA, vir-like m6A methyltransferase-associated; HAKAI, E3 ubiquitin-protein ligase Hakai (also known as CBLL1, cbl proto-oncogene-like 1); ZC3H13, zinc finger CCCH-type containing 13 proteins; FTO, fat-mass and obesity-associated protein; ALKBH5, alkB homolog 5; YTHDF, YT521-B homology domain family; FMRP, fragile X mental retardation protein; hnRNPA2/B1, heterogeneous nuclear ribonucleoprotein A2/B1; PRRC2A, proline rich coiled-coil 2A; IGF2BP1/2/3, insulin like growth factor 2 mRNA binding protein 1/2/3; elF3, E74-like factor 3