N6-Methyladenosine

N⁶-Methyladenosine

Names
IUPAC name N-Methyladenosine
Other names m6A
Identifiers
CAS Number	1867-73-8
3D model (JSmol)	Interactive image
ChemSpider	92307
PubChem CID	102175
InChI InChI=1S/C11H15N5O4/c1-12-9-6-10(14-3-13-9)16(4-15-6)11-8(19)7(18)5(2-17)20-11/h3-5,7-8,11,17-19H,2H2,1H3,(H,12,13,14)/t5-,7-,8-,11-/m1/s1 Key: VQAYFKKCNSOZKM-IOSLPCCCSA-N InChI=1/C11H15N5O4/c1-12-9-6-10(14-3-13-9)16(4-15-6)11-8(19)7(18)5(2-17)20-11/h3-5,7-8,11,17-19H,2H2,1H3,(H,12,13,14)/t5-,7-,8-,11-/m1/s1 Key: VQAYFKKCNSOZKM-IOSLPCCCBA
SMILES n2c1c(ncnc1NC)n(c2)[C@@H]3O[C@@H]([C@@H](O)[C@H]3O)CO
Properties
Chemical formula	C11H15N5O4
Molar mass	281.27 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

N⁶-Methyladenosine (m⁶A) is an abundant modification in mRNA and is found within some viruses, and most eukaryotes including mammals, insects, plants and yeast. It is also found in tRNA, rRNA, and small nuclear RNA (snRNA) as well as several long non-coding RNA, such as Xist.

Adenosine methylation is directed by a large m⁶A methyltransferase complex containing METTL3 as the SAM-binding sub-unit.In vitro, this methyltransferase complex preferentially methylates RNA oligonucleotides containing GGACU and a similar preference was identified in vivo in mapped m⁶A sites in Rous sarcoma virus genomic RNA and in bovine prolactin mRNA. More recent studies have characterized other key components of the m⁶A methyltransferase complex in mammals, including METTL14, Wilms tumor 1 associated protein (WTAP) and KIAA1429. Following a 2010 speculation of m⁶A in mRNA being dynamic and reversible, the discovery of the first m⁶A demethylase, fat mass and obesity-associated protein (FTO) in 2011 confirmed this hypothesis and revitalized the interests in the study of m⁶A. A second m⁶A demethylase alkB homolog 5 (ALKBH5) was later discovered as well.

The biological functions of m⁶A are mediated through a group of RNA binding proteins that specifically recognize the methylated adenosine on RNA. These binding proteins are named m⁶A readers. The YT521-B homology (YTH) domain family of proteins (YTHDF1, YTHDF2, YTHDF3 and YTHDC1) have been characterized as direct m⁶A readers and have a conserved m⁶A-binding pocket. These m⁶A readers, together with m⁶A methyltransferases (writers) and demethylases (erasers), establish a complex mechanism of m⁶A regulation in which writers and erasers determine the distributions of m⁶A on RNA, whereas readers mediate m⁶A-dependent functions. m⁶A has also been shown to mediate a structural switch termed m⁶A switch.

In budding yeast (Sacharomyces cerevisiae), the homologue of METTL3, IME4 is induced in diploid cells in response to nitrogen and fermentable carbon source starvation and is required for mRNA methylation and the initiation of correct meiosis and sporulation. mRNAs of IME1 and IME2, key early regulators of meiosis, are known to be targets for methylation, as are transcripts of IME4 itself.