METTL16
Domain
The VCR (vertebrate conserved) regions bind the first hairpin of MAT2A mRNAs (PubMed:28525753). The VCR regions interact with the internal stem-loop within U6 snRNAs, inducing the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the methyltransferase region (PubMed:32266935).
The K-loop region occludes the S-adenosyl-L-methionine-binding pocket (PubMed:30197297). Upon activation, conformation of the K-loop changes, allowing S-adenosyl-L-methionine-binding (PubMed:30197297).
Function
RNA N6-methyltransferase that methylates adenosine residues at the N(6) position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts (PubMed:28525753, PubMed:30197297, PubMed:30197299, PubMed:33428944, PubMed:33930289). Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs) (PubMed:28525753). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure (PubMed:28525753, PubMed:30197297, PubMed:30197299). Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby inhibiting splicing and protein production of S-adenosylmethionine synthase (PubMed:28525753, PubMed:33930289). In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A (PubMed:28525753). In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs (PubMed:28525753, PubMed:29051200, PubMed:32266935). Also able to bind various lncRNAs, such as 7SK snRNA (7SK RNA) or 7SL RNA (PubMed:29051200). Specifically binds the 3'-end of the MALAT1 long non-coding RNA (PubMed:27872311).
Sequence Similarities
Belongs to the methyltransferase superfamily. METTL16/RlmF family.
Cellular localization
- Nucleus
- Cytoplasm
Alternative names
METT10D, METTL16, RNA N(6)-adenosine-methyltransferase METTL16, Methyltransferase 10 domain-containing protein, Methyltransferase-like protein 16, U6 small nuclear RNA (adenine-(43)-N(6))-methyltransferase