N6-adenosine-methyltransferase non-catalytic subunit

Definition:

The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis. In the heterodimer formed with METTL3, METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability and processing. M6A acts as a key regulator of mRNA stability by promoting mRNA destabilization and degradation (By similarity). In embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization (By similarity). M6A regulates spermatogonial differentiation and meiosis and is essential for male fertility and spermatogenesis (By similarity). M6A also regulates cortical neurogenesis: m6A methylation of transcripts related to transcription factors, neural stem cells, the cell cycle and neuronal differentiation during brain development promotes their destabilization and decay, promoting differentiation of radial glial cells (By similarity).

References:

[1]. Paweł Śledź, et al. Structural insights into the molecular mechanism of the m(6)A writer complex. Elife. 2016 Sep 14;5:e18434. [Content Brief]

[2]. Xiang Wang, et al. Structural basis of N(6)-adenosine methylation by the METTL3-METTL14 complex. Nature. 2016 Jun 23;534(7608):575-8. [Content Brief]

[3]. Jianzhao Liu, et al. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol. 2014 Feb;10(2):93-5. [Content Brief]

[4]. Ping Wang, et al. Structural Basis for Cooperative Function of Mettl3 and Mettl14 Methyltransferases. Mol Cell. 2016 Jul 21;63(2):306-317. [Content Brief]

[5]. Xiao-Li Ping, et al. Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 2014 Feb;24(2):177-89. [Content Brief]

[6]. Nian Liu, et al. N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature. 2015 Feb 26;518(7540):560-4. [Content Brief]

[7]. Eva Schöller, et al. Interactions, localization, and phosphorylation of the m6A generating METTL3-METTL14-WTAP complex. RNA. 2018 Apr;24(4):499-512. [Content Brief]

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