Abstract
Antisense (as)lncRNAs can regulate gene expression but whether this occurs at the transcriptional or post-transcriptional level remains unclear. Furthermore, the molecular bases for aslncRNAs-mediated regulation remain incomplete. Here, we report that inactivation of the cytoplasmic exoribonuclease Exo2 results confers sensitivity to oxidative stress in fission yeast. Mechanistic investigations revealed that induction of the catalase-coding gene ctt1 is impaired in exo2Δ cells, correlating with the accumulation an Exo2-sensitivite lncRNA (XUT), antisense to ctt1. Interestingly, expression of the asXUT was also activated in wild-type cells upon oxydative stress, concomitant to ctt1 induction, indicating a potential attenuation feedback. This attenuation is Dicer-independent, characterized by low RNAPII-ser5 phosphorylation and requires histone deacetylase activity. Using Native Elongating Transcript sequencing in exo2Δ, we revealed asXUT-associated attenuation for a subset of highly transcribed genes displaying prominent promoter-proximal nucleosome depletion and histone acetylation, suggesting that asXUTs attenuate genes whose transcription exceeds a critical threshold. We propose that asXUT could mediate transcriptional regulation via sense-paired gene promoter features using a general conserved mechanism, independent of RNAi.
