Genetic and environmental perturbations alter the rhythmic expression pattern of a circadian long non-coding RNA, Per2AS, in mouse liver.
Genetic and environmental perturbations alter the rhythmic expression pattern of a circadian long non-coding RNA, Per2AS, in mouse liver.
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DOI：
10.12688/f1000research.125628.2
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发表时间：
2022
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背景：长的非编码RNA(LncRNAs)在不编码蛋白质的情况下发挥着广泛的生物学作用。尽管近年来许多lncRNAs的功能已被发现，但尽管与mRNAs相比，lncRNAs的表达模式更具特异性，但对lncRNAs表达的调控机制仍知之甚少。在这里，我们研究了Per2AS的节律性表达，Per2AS是一种新的调节昼夜节律的IncRNA。由于Per2AS的表达与核心生物钟基因Perod2(PER2)相反，并且是从PER2的反义链转录而来的，我们假设Per2AS的有节奏的表达要么是由它自己的启动子驱动的，要么是由PER2的有节奏的转录通过转录干扰来驱动的。方法：我们利用现有的昼夜节律RNA-seq数据集，分析了Per2AS和PER2基因的表达模式，以响应小鼠肝脏昼夜节律的遗传或环境干扰。我们通过比较Per2AS和PER2表达模式的变化来检验我们的假设。结论：我们发现，在某些情况下，Per2AS的表达独立于其他昼夜节律转录因子控制。在其他情况下，表达变化的模式与转录干扰和独立调控假说是一致的。虽然需要更多的实验来区分这些可能性，但这项工作的发现有助于更深入地理解lncRNA表达是如何调控的机制。
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.