Discovery of an mRNA 5'-end capping quality control mechanism

Updated Jan. 2023

mRNAs are capped at the 5'-end (m7Gppp) during the early stage of Pol II transcription. The cap protects the mRNA and is essential for translation.

The capping process involves 3 steps: The primary transcript from Pol II, with a 5' triphosphate group (pppRNA), is converted to ppRNA. GMP is then linked to the RNA, through a 5'-5' connection, to make the capped RNA (GpppRNA). Finally, a methyltransferase methylates the 7 position of guanine to produce the mature cap (m7GpppRNA).

It is generally believed that capping is a default process, in that it always proceeds to completion. A quality control mechanism for 5' capping was not known.

In our studies on the Rat1-Rai1 complex, we unexpectedly discovered that Rai1 has an active site of its own. Biochemical experiments demonstrated that Rai1 possesses RNA 5' pyrophosphohydrolase (PPH) activity, providing the first hint that there may be involved in 5' capping quality control in eukaryotes.

Rai1 has sequence homologs from yeast to humans, and the mammalian homolog is known as Dom3Z. However, the sequence conservation is very weak, only a few residues are strictly conserved among these proteins.

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