Transcription & RNA

5' cap

/ FYV-prym KAP /

Imagine mailing a fragile document. Before it leaves your hands you seal one end so it cannot get chewed up in transit and so the recipient knows it is genuine and where to start reading. The 5-prime cap is exactly that kind of seal for a messenger RNA. It is a special chemical group added to the very front end (the 5-prime end) of the RNA, very soon after transcription begins.

Chemically, the cap is a modified guanine nucleotide (specifically 7-methylguanosine) joined to the front of the RNA by an unusual linkage that runs backward compared to the rest of the chain. That odd backward linkage is the trick: ordinary RNA-chewing enzymes cannot grab the capped end, so the cap shields the message from being degraded from the front. The cap is added co-transcriptionally — that is, while transcription is still going on — making it the first processing event a eukaryotic transcript undergoes.

The cap earns its keep in three ways. It protects the RNA from rapid breakdown, it serves as a handle the cell uses to ship the RNA out of the nucleus, and it is the docking signal the ribosome recognizes to begin translation. An uncapped mRNA is both vulnerable and largely ignored by the protein-making machinery — which is one reason cells, and clever vaccine designers, pay close attention to getting the cap right.

The mRNA COVID vaccines work only because each mRNA carries a proper 5' cap; without it, your cells would shred the vaccine RNA almost immediately and would not bother translating it into the spike protein that trains your immune system.

mRNA vaccines need a correct 5' cap to survive in the cell and get translated.

The cap sits at the 5' (front) end and the poly-A tail at the 3' (back) end — two different protections on opposite ends of the same mRNA. Do not mix them up.

Also called
5-prime cap7-methylguanosine capm7G cap甲基鸟苷帽