We identified PCIF1 as a cap-specific adenosine methyltransferase for m6Am
Our new paper named ” Cap-specific, terminal N6-methylation by a mammalian m6Am methyltransferase ” has been published in Cell Research (https://www.nature.com/articles/s41422-018-0117-4).
RNA modifications have been found to regulate gene expression, leading to the field of Epitranscriptomics. The first m6A demethylase FTO also catalyzed the demethylation of m6Am, so m6Am is a dynamic and reversible RNA methylation. However, little is known about its methylase and function. In this study we revealed the exact identity of PCIF1, a factor that interacts with phosphorylated CTD of RNA polymerase II, as the m6Am writer protein. We characterized the biochemical property and substrate preference of PCIF1, and profiled its cellular targets using an epitranscriptomic sequencing approach. PCIF1 recognizes the positively charged cap structure m7GpppAm for optimal activity and is a “stand-alone” RNA methyltransferase. We envision that the identification of PCIF1 as the m6Am writer will pave the path toward functional and mechanistic dissection of this dynamic and reversible epitranscriptomic mark in the future.
