Xumei Chen: 5' Capping of RNA by cellular metabolites

In eukaryotes, messenger RNAs (mRNAs) harbor a 5’ methylguanosine (m⁷G) cap, which stabilizes mRNAs and assists with their processing, nuclear export and translation. In recent years, it has come to be realized that cellular metabolites, such as NAD⁺, dpCoA, FAD, UDP-glucose and UDP-GlcNAc, etc., can serve as noncanonical RNA caps in prokaryotes and eukaryotes. These metabolites are thought to be incorporated into RNA as the initiating nucleotide during transcription. The caps can also be removed by decapping enzymes, some acting on many noncanonical caps while others are highly specific. To begin to understand the molecular and biological functions of the noncanonical caps, we are developing various technologies to detect and quantify these noncanonical RNA caps and methods to profile RNAs with these metabolite caps, and identify decapping enzymes that specifically target one type of RNA cap. I will mainly discuss progress made towards characterizing RNAs with the dpCoA cap and hope to initiate collaborations with colleagues to explore the functions of dpCoA-RNA in various biological contexts.