Onofrio Zanin, Matthew Eastham, Kinga Winczura, Mark Ashe, Rocio T. Martinez-Nunez, Daniel Hebenstreit and Pawel Grzechnik

Most functional eukaryotic mRNAs contain a 5’ 7-methylguanosine (m7 G) cap. Although capping is essential for many biological processes,the fate of uncapped transcripts has not been studied extensively. Here, we employed fast nuclear depletion of the capping enzymes in Saccharomyces cerevisiae to uncover the turnover of the transcripts that failed to be capped. We show that although the degradation of cap-deficient mRNA is dominant, the levels of hundreds of non-capped mRNAs increase upon depletion of the capping enzymes. Overall, the abundance of non-capped mRNAs is inversely correlated to the expression levels, altogether resembling the effects observed in cells lacking the cytoplasmic 5’-3’ exonuclease Xrn1 and indicating differential degradation fates of non-capped mRNAs. Our data indicate that the cap presence is essential to initiate the Xrn1-dependent degradation of mRNAs underpinning the role of 5’ cap in the Xrn1-dependent buffering of the cellular mRNA levels.

Communications Biology. November 2023