Cap-Specific mAm Methyltransferase PCIF1/CAPAM Regulates mRNA Stability of and through the mA Methyltransferase Activity.

Chemical modifications of cellular RNAs play key roles in gene expression and host defense. The cap-adjacent ,2'--dimethyladenosine (mAm) is a prevalent modification of vertebrate and viral mRNAs and is catalyzed by the newly discovered methyltransferase PCIF1. However, its role in gene expression remains unclear due to conflicting reports on its effects on mRNA stability and translation.

The cap-specific m6A methyltransferase, PCIF1/CAPAM, is dynamically recruited to the gene promoter in a transcription-dependent manner.

N 6-methyladenosine (m6A), the most abundant modification in eukaryotic mRNAs, plays an important role in mRNA metabolism and functions. When adenosine is transcribed as the first cap-adjacent nucleotide, it is methylated at the ribose 2'-O and N6 positions, thus generating N6, 2'-O-dimethyladenosine (m6Am). Phosphorylated C-terminal domain (CTD)-interacting factor 1 (PCIF1) is a novel cap-specific adenine N6-methyltransferase responsible for m6Am formation.