Antisense RNA Stabilization Induces Transcriptional Gene Silencing via Histone Deacetylation in S. cerevisiae

Abstract

Genome-wide studies in S. cerevisiae reveal that the transcriptome includes numerous antisense RNAs as well as intergenic transcripts regulated by the exosome component Rrp6. We observed that upon the loss of Rrp6 function, two PHO84 antisense transcripts are stabilized, and PHO84 gene transcription is repressed. Interestingly, the same phenotype is observed in wild-type cells during chronological aging. Epistasis and chromatin immunoprecipitation experiments indicate that the loss of Rrp6 function is paralleled by the recruitment of Hda1 histone deacetylase to PHO84 and neighboring genes. However, histone deacetylation is restricted to PHO84, suggesting that Hda1 activity depends on antisense RNA. Accordingly, the knockdown of antisense production prevents PHO84 gene repression, even in the absence of Rrp6. Together, our data indicate that the stabilization of antisense transcripts results in PHO84 gene repression via a mechanism distinct from transcription interference and that the modulation of Rrp6 function contributes to gene regulation by inducing RNA-dependent epigenetic modifications.

Divergent transcription: A new feature of active promoters

“…55,56 The generality of ncRNAs modulating transcription from promoters in their immediate vicinity is unknown, but these results suggest that DNA associated RNAs can be the targets of RNA binding proteins which interact with chromatin modifying enzymes and lead to changes in gene expression level.…”

A de novo originated gene depresses budding yeast mating pathway and is repressed by the protein encoded by its antisense strand

“…TI was thought to be an unavoidable suppressive consequence of two convergent promoters directing transcripts that overlap for at least part of their sequences [4]. But in the case of PHO84, the sense gene is regulated by accumulation of antisense RNAs, which leads to targeted histone deacetylation and the silencing of sense transcription [5]. However, all the reported mechanisms rely on the noncoding antisense RNAs.…”

LncRNAs: Bridging environmental sensing and gene expression

“…Finally, as more efforts are put forth to decipher the role of the non-coding genome, it must be emphasized that some of these long non-coding RNAs have been detected with translating ribosomes. 88 Although no examples of lncRNAs that produce functional peptides have been documented to date, we should continue to view the term 29 Promotes induction MMF1 Mitochondrial protein YES ASP3 lncRNA 98 Upregulation ASP3 Asparagine catabolism YES PHO84 AS RNA [99][100][101] Repression PHO84 Phosphate metabolism YES SRG1 28,50,51 Repression SER3 Serine / glycine biogenesis YES PHO5 AS RNA 102 Promotes induction PHO5 Phosphate metabolism YES usURA2. 103 Repression URA2 Pyrimidine biogenesis YES usDCI1.…”