Nonsense-Mediated Decay Restricts LncRNA Levels in Yeast Unless Blocked by Double-Stranded RNA Structure

Mol Cell. 2016 Feb 4;61(3):379-392. doi: 10.1016/j.molcel.2015.12.020. Epub 2016 Jan 21.


Antisense long non-coding (aslnc)RNAs represent a substantial part of eukaryotic transcriptomes that are, in yeast, controlled by the Xrn1 exonuclease. Nonsense-Mediated Decay (NMD) destabilizes the Xrn1-sensitive aslncRNAs (XUT), but what determines their sensitivity remains unclear. We report that 3' single-stranded (3'-ss) extension mediates XUTs degradation by NMD, assisted by the Mtr4 and Dbp2 helicases. Single-gene investigation, genome-wide RNA analyses, and double-stranded (ds)RNA mapping revealed that 3'-ss extensions discriminate the NMD-targeted XUTs from stable lncRNAs. Ribosome profiling showed that XUT are translated, locking them for NMD activity. Interestingly, mutants of the Mtr4 and Dbp2 helicases accumulated XUTs, suggesting that dsRNA unwinding is a critical step for degradation. Indeed, expression of anticomplementary transcripts protects cryptic intergenic lncRNAs from NMD. Our results indicate that aslncRNAs form dsRNA that are only translated and targeted to NMD if dissociated by Mtr4 and Dbp2. We propose that NMD buffers genome expression by discarding pervasive regulatory transcripts.

Keywords: NMD; RNA helicases; Xrn1; dsRNA; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism
  • Gene Expression Regulation, Fungal
  • Genome, Fungal
  • Mutation
  • Nonsense Mediated mRNA Decay*
  • Nucleic Acid Conformation
  • Open Reading Frames
  • RNA, Antisense / genetics
  • RNA, Antisense / metabolism
  • RNA, Double-Stranded / chemistry
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism*
  • RNA, Fungal / chemistry
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism*
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic


  • RNA, Antisense
  • RNA, Double-Stranded
  • RNA, Fungal
  • RNA, Long Noncoding
  • Saccharomyces cerevisiae Proteins
  • Exoribonucleases
  • XRN1 protein, S cerevisiae
  • Dbp2 protein, S cerevisiae
  • MTR4 protein, S cerevisiae
  • DEAD-box RNA Helicases