METTL1
Description
The METTL1 (methyltransferase 1, tRNA methylguanosine) is a protein-coding gene located on chromosome 12.
METTL1 is a human gene encoding tRNA (guanine-N(7)-)-methyltransferase, an enzyme involved in RNA methylation. The gene shares sequence similarity with the S. cerevisiae YDL201w gene and contains a conserved S-adenosylmethionine-binding motif. It is inactivated by phosphorylation and produces various protein isoforms through alternative splicing. Different transcript variants utilizing alternative polyA sites have also been reported.
METTL1 is a catalytic component of the METTL1-WDR4 methyltransferase complex. This complex mediates the formation of N(7)-methylguanine in a subset of RNA species, including tRNAs, mRNAs, and microRNAs (miRNAs). Specifically, METTL1 catalyzes the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop. This modification stabilizes tRNA tertiary structure by interacting with C13-G22 in the D-loop and protects tRNAs from decay. METTL1 also acts as a methyltransferase for a subset of internal N(7)-methylguanine in mRNAs, promoting their relocalization to stress granules under stress conditions, thereby suppressing their translation. Additionally, METTL1 methylates a specific subset of miRNAs, such as let-7, promoting let-7 miRNA processing by disrupting an inhibitory secondary structure within the primary miRNA transcript (pri-miRNA). METTL1 is also implicated in the regulation of embryonic stem cell self-renewal and differentiation.
METTL1 is also known as C12orf1, TRM8, TRMT8, YDL201w.
