N7methyltransferase

N7-methyltransferase is an enzyme family that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to the N7 position of the guanine base in RNA. The catalytic step forms the 7-methylguanosine cap (m7G) at the 5' end of RNA, typically converting a cap structure from GpppN to m7GpppN. This modification is a key feature of eukaryotic mRNA and certain small RNAs, and it plays a central role in RNA stability and processing.

In eukaryotes, N7-methylation is part of the mRNA capping pathway that occurs early during transcription. The m7G cap is recognized by cap-binding proteins and is important for efficient splicing, nuclear export, and translation initiation. The canonical cytoplasmic/mammalian enzyme is RNMT, which often functions in a complex with RAM (RNMT Activating Mini Protein). In yeast, the corresponding enzyme is Abd1. Some viruses and other organisms encode related N7-methyltransferases, including the coronavirus nsp14, which provides cap formation activity in conjunction with other methyltransferases.

Biochemically, N7-methyltransferases are SAM-dependent methyltransferases and typically exhibit a Rossmann-like fold. Substrate recognition focuses on the RNA cap structure, and activity is regulated by subcellular localization, interaction with partner proteins, and cellular levels of SAM and SAH.

Clinical and research relevance centers on the essential nature of cap methylation for gene expression. Disruptions in N7-methyltransferase activity can impair mRNA translation and stability, while viral enzymes represent potential targets for antiviral therapy. Inhibitors and modulators of cap methylation are active areas of study in molecular biology and drug development.