Extensive 5'-surveillance guards against non-canonical NAD-caps of nuclear mRNAs in yeast

Nat Commun. 2020 Nov 2;11(1):5508. 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 of transcripts is low (<5%). NAD incorporation occurs mainly during transcription initiation 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 are not translatable in vitro. Our work indicates that in budding yeast, most of the NAD incorporation into RNA seems to be disadvantageous to the cell, which has evolved a diverse surveillance machinery to prematurely terminate, decap and reject NAD-RNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Cell Nucleus / genetics
  • Endoribonucleases / metabolism*
  • NAD / metabolism*
  • Pyrophosphatases / metabolism
  • RNA Caps / metabolism*
  • RNA Stability
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / metabolism
  • Ribosomes / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic


  • 5' Untranslated Regions
  • RNA Caps
  • RNA, Messenger
  • RNA-Binding Proteins
  • Rai1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • mRNA decapping enzymes
  • NAD
  • Endoribonucleases
  • NPY1 protein, S cerevisiae
  • Pyrophosphatases