Yu, Dan; Zhou, Jujun; Chen, Qin; Wu, Tao; Blumenthal, Robert M; Zhang, Xing; Cheng, Xiaodong
description
PCIF1 and FTO are a pair of human mRNA cap-specific modification enzymes that have opposing activities. PCIF1 adds a methyl group to the N6-position of 2'-methyladenosine (A), generating N6, 2'-dimethyladenosine (mA), when A is the cap-proximal nucleotide. FTO removes the N6-methyl group from mA. In addition, FTO has a demethylase activity on a broad spectrum of various RNA substrates, as well as on NA N6-methyldeoxyadenosine (mdA). While the existence of mdA in mammalian NA remains controversial, we show here that PCIF1 has significant methylation activity on single stranded DNA deoxyadenosine, double stranded RNA/DNA hybrids, and double stranded DNA, though with lower catalytic efficiency than that on its preferred RNA substrate. PCIF1 has activities in the order ssRNA > RNA/DNA hybrid > ssDNA > dsDNA. We discuss the implications of PCIF1 generation, and FTO removal, of DNA adenine methylation.
