m7GpppNm

m7GpppNm is a designation used in molecular biology to describe a specific 5' cap structure found on many eukaryotic mRNAs. The name reflects two key features: a 7-methylguanosine moiety (m7G) linked via a triphosphate bridge (ppp) to the first transcribed nucleotide, and a 2'-O-methyl modification (the “m” in Nm) on the ribose of that first nucleotide. The N in Nm stands for the first nucleotide, which can be any of the four bases (adenine, cytosine, guanine, or uracil).

Chemical structure and formation

The core cap structure is formed early in transcription by capping enzymes that add m7G via a 5'–5' triphosphate linkage to the nascent RNA, producing m7GpppN (cap0). The first nucleotide after the cap often undergoes 2'-O-methylation of its ribose, a reaction carried out by cap-specific methyltransferases such as CMTR1, yielding the cap1 structure, m7GpppNm. In some transcripts, further 2'-O-methylation can occur on subsequent nucleotides, producing cap2 variants.

Biological significance

The m7GpppNm cap variant plays a crucial role in RNA metabolism. It protects the transcript from 5' exonucleases, enhances splicing and nuclear export, and facilitates efficient initiation of translation by promoting recognition by cap-binding proteins and the translation machinery. The cap structure also influences innate immune sensing of RNA.

Occurrence and variation

m7GpppNm is common in mature eukaryotic mRNAs and is one of several cap configurations, with cap0 (m7GpppN) and cap2 being related forms that differ in the extent of 2'-O-methylation. The specific pattern of cap methylation can affect gene expression and RNA stability across different organisms and tissues.