m7GpppN

m7GpppN is the canonical 5' cap structure found on most eukaryotic mRNAs and many noncoding RNAs. It consists of a 7-methylguanosine (m7G) residue linked to the RNA via a 5'-5' triphosphate bridge to the first transcribed nucleotide, denoted N. In standard notation the cap is written as m7GpppN, where N is the first nucleotide of the transcript. The basic cap is often called Cap0; additional methylation on the ribose of the first nucleotide forms Cap1 (m7GpppNm), and sometimes Cap2 (m7GpppNmN).

Biosynthesis of the cap occurs co-transcriptionally through a multistep process. A RNA triphosphatase removes the gamma phosphate from the nascent 5' end, creating a diphosphate end. A guanylyltransferase then adds GMP from GTP to form GpppN. A guanine-N7 methyltransferase (RNMT in mammals) methylates the added guanine at the N7 position to yield m7GpppN. In many organisms, 2'-O-methyltransferases (such as CMTR1) modify the ribose of the first nucleotide to form Cap1; further 2'-O-methylation can produce Cap2. The capping enzymes are part of a conserved capping complex, such as RNGTT in humans (and Cet1/Ceg1 in yeast).

Functions and significance of the cap include promotion of translation initiation via cap-binding proteins (notably eIF4E), enhancement of mRNA splicing and export, and protection from 5' exonucleases. The cap also helps distinguish self from non-self RNA, influencing innate immune recognition. Many viruses employ cap-snatching or alternative capping strategies to mimic or acquire m7GpppN structures for their transcripts.

Occurrence and variants: Cap0, Cap1, and Cap2 structures are common in eukaryotes, with Cap1/2 involving 2'-O-methylation on the first (and sometimes second) nucleotides. The m7GpppN motif is a defining feature of mature cytoplasmic mRNA and related RNAs, essential for proper RNA metabolism and gene expression.