Methyltransferase-like protein 3 and methyltransferase-like protein 14 are the two catalytic subunits of an N6-methyltransferase complex that methylates adenosine residues in RNA. Methylation of adenosine residues regulates mRNA splicing, processing, translation efficiency, editing and stability, in addition to regulating primary miRNA processing, and is critical for proper regulation of the circadian clock, embryonic stem cell self-renewal, immune tolerance, response to various stimuli, meiosis and mouse fertility. In this complex, METTL3 functions as the catalytic methyltransferase subunit and METTL14 functions as the target recognition subunit by binding to RNA. In addition, the Wilms' tumor 1-associating protein functions as a regulatory subunit and is required for accumulation of the complex to nuclear speckles, which are sites of RNA processing. Several studies suggest a role for this complex in cancer. METTL3 expression is elevated in lung adenocarcinoma where it promotes growth, survival, and invasion of human lung cancer cells. In addition, WTAP is overexpressed in a number of different cancers and positively regulates cell migration and invasion in glioblastoma and cholangiocarcinoma.
[1] Liu, J. et al. (2014) Nat Chem Biol 10, 93-5.
[2] Yue, Y. et al. (2015) Genes Dev 29, 1343-55.
[3] Wu, R. et al. (2016) Mol Biotechnol 58, 450-9.
[4] Wang, X. et al. (2016) Nature 534, 575-8.
[5] Ping, X.L. et al. (2014) Cell Res 24, 177-89.
[6] Lin, S. et al. (2016) Mol Cell 62, 335-45.
[7] Jin, D.I. et al. (2012) Cancer Sci 103, 2102-9.
[8] Jo, H.J. et al. (2013) J Gastroenterol 48, 1271-82.
