Genetic and environmental perturbations alter the rhythmic expression pattern of a circadian long non-coding RNA, Per2AS, in mouse liver [version 2; peer review: 2 approved]

Abstract

Background: Long non-coding RNAs (lncRNAs) play a wide variety of biological roles without encoding a protein. Although the functions of many lncRNAs have been uncovered in recent years, the regulatory mechanism of lncRNA expression is still poorly understood despite that the expression patterns of lncRNAs are much more specific compared to mRNAs. Here, we investigated the rhythmic expression of Per2AS, a novel lncRNA that regulates circadian rhythms. Given that Per2AS expression is antiphasic to Period2 (Per2), a core circadian clock gene, and transcribed from the antisense strand of Per2, we hypothesized that the rhythmic Per2AS expression is driven either by its own promoter or by the rhythmic Per2 transcription via transcriptional interference. Methods: We leveraged existing circadian RNA-seq datasets and analyzed the expression patterns of Per2AS and Per2 in response to the genetic or environmental disruption of the circadian rhythm in mouse liver. We tested our hypotheses by comparing the changes in the expression patterns of Per2AS and Per2. Conclusions: We found that, in some cases, Per2AS expression is independently controlled by other circadian transcription factors. In other cases, the pattern of expression change is consistent with both transcriptional interference and independent regulation hypotheses. Although additional experiments will be necessary to distinguish these possibilities, findings from this work contribute to a deeper understanding of the mechanism of how the expression of lncRNA is regulated.

Keywords

• LncRNAs
• circadian rhythm
• antisense
• rhythmicity
• feeding regimen
• eng