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Extensive 5'-Surveillance Guards Against Non-Canonical NAD-Caps of Nuclear mRNAs in Yeast

By Yaqing Zhang, David Kuster, Tobias Schmidt, Daniel Kirrmaier, Gabriele Nübel, David Ibberson, Vladimir Benes, Hans Hombauer, Michael Knop, Andres Jäschke

Posted 28 Apr 2020
bioRxiv DOI: 10.1101/2020.04.28.065920 (published DOI: 10.1038/s41467-020-19326-3)

The ubiquitous redox coenzyme nicotinamide adenine dinucleotide (NAD) acts as a non-canonical cap structure on prokaryotic and eukaryotic ribonucleic acids. Here we find that in budding yeast, NAD-RNAs are abundant (>1400 species), short (<170 nt), and mostly correspond to mRNA 5'-ends. The modification percentage is low (<5%). NAD is incorporated during the initiation step by RNA polymerase II, which uses distinct promoters with a YAAG core motif for this purpose. Most NAD-RNAs are 3'-truncated. At least three decapping enzymes, Rai1, Dxo1, and Npy1, guard against NAD-RNA at different cellular locations, targeting overlapping transcript populations. NAD-mRNAs do not support translation in vitro. Our work indicates that in budding yeast, most of the NAD incorporation into RNA seems to be accidental and undesirable to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs. ### Competing Interest Statement The authors have declared no competing interest.

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