The role of Nonsense-Mediated mRNA Decay in restricting long noncoding RNAs expression has been conserved in RNAi-capable budding yeast

ABSTRACT: In most Eukaryotes, sense/antisense RNA duplexes can be processed into small interfering RNAs by the ribonuclease III Dicer, a key component of the RNA interference (RNAi) machinery, which has been lost by the budding yeast Saccharomyces cerevisiae. Previous studies in this species revealed the pervasive formation of double-stranded (ds)RNA involving antisense Xrn1-sensitive long noncoding (lnc)RNAs, which interferes with their degradation through translation-dependent Nonsense-Mediated mRNA decay (NMD). However, apart from S. cerevisiae, little is known about the post-transcriptional metabolism of lncRNAs, in particular the functional impact of RNAi. Herein, we profiled NMD targets in Naumovozyma castellii, a budding yeast endowed with cytoplasmic RNAi. We identified 592 lncRNAs accumulating in a mutant of the NMD core factor Upf1. Most of them also accumulate in other NMD mutants and upon translation elongation inhibition, indicating a translation-dependent degradation mechanism. Consistently, Ribo-Seq analyses confirmed ribosomes binding for a fraction of them. Within the coding transcriptome, we found that the Dicer-coding mRNA is also regulated by NMD. The resulting upregulation of DCR1 in NMD-deficient cells correlates with an increased production of small RNAs from dsRNA-forming NMD-sensitive lncRNAs and mRNAs. Finally, we observed that Dicer inactivation in Upf1-lacking cells attenuates the accumulation of dsRNA-forming NMD targets. Together, our data highlight the conserved roles of NMD and translation in the post-transcriptional metabolism of lncRNAs, and provide insight into the functional impact of endogenous RNAi on the transcriptome.

ORGANISM(S): Naumovozyma castellii

PROVIDER: GSE291712 | GEO | 2025/10/01

REPOSITORIES: GEO