Bases of antisense lncRNA-associated regulation of gene expression in fission yeast

Abstract

Antisense (as)lncRNAs can regulate gene expression but the underlying mechanisms and the different cofactors involved remain unclear. Using Native Elongating Transcript sequencing, here we show that stabilization of antisense Exo2-sensitivite lncRNAs (XUTs) results in the attenuation, at the nascent transcription level, of a subset of highly expressed genes displaying prominent promoter-proximal nucleosome depletion and histone acetylation. Mechanistic investigations on the catalase gene ctt1 revealed that its induction following oxidative stress is impaired in Exo2-deficient cells, correlating with the accumulation of an asXUT. Interestingly, expression of this asXUT was also activated in wild-type cells upon oxidative stress, concomitant to ctt1 induction, indicating a potential attenuation feedback. This attenuation correlates with asXUT abundance, it is transcriptional, characterized by low RNAPII-ser5 phosphorylation, and it requires an histone deacetylase activity and the conserved Set2 histone methyltransferase. Finally, we identified Dicer as another RNA processing factor acting on ctt1 induction, but independently of Exo2. We propose that asXUTs could modulate the expression of their paired-sense genes when it exceeds a critical threshold, using a conserved mechanism independent of RNAi.

The how and why of lncRNA function: An innate immune perspective

“…Furthermore, the function of lncRNAs can often be dictated by their localization, sequence and/or secondary structure. There are many categories and sub-categories of lncRNAs, but some of the major classifications include: antisense [6], bi-directional [7], enhancer-associated [8], intergenic lncRNAs (lincRNAs) [9], pseudogenes [10], while a full review of all classifications can be obtained from the recent review by Jarroux et al [11]. LncRNA function cannot be determined simply based on the lncRNA classification.…”

Endogenous RNAi pathway evolutionarily shapes the destiny of the antisense lncRNAs transcriptome

“…Among them, the 'antisense' (as)lncRNAs are synthesized from the strand opposite to 'sense' protein-coding genes (Pelechano and Steinmetz 2013) and have attracted a lot of attention given their potential to regulate gene expression (Kopp and Mendell 2018). In fact, examples of aslncRNA-mediated regulation of gene expression have been reported in different organisms, including the budding yeast Saccharomyces cerevisiae (Camblong et al 2007;Uhler et al 2007;Berretta et al 2008;Houseley et al 2008;Camblong et al 2009;Pinskaya et al 2009;Van Dijk et al 2011;van Werven et al 2012), the fission yeast Schizosaccharomyces pombe (Wery et al 2018a), plants (Swiezewski et al 2009) and…”

From Yeast to Mammals, the Nonsense-Mediated mRNA Decay as a Master Regulator of Long Non-Coding RNAs Functional Trajectory

“…In budding and fission yeasts, cytoplasmic lncRNAs are extensively degraded by the 5 -3 exoribonuclease Xrn1/Exo2 [124,[137][138][139]. Inactivation of Xrn1 leads to the stabilization of Xrn1-sensititve Unstable Transcripts (XUTs), the majority of which are antisense to protein-coding genes [124,[138][139][140].…”