Circadian Oscillation of Natural Antisense Transcripts Related to Human Core Clock Genes

Parisa Najari Hanjani,Masoud Golalipour

doi:10.52547/rbmb.10.3.471

Abstract

Circadian clocks are autonomous intracellular oscillators that synchronize metabolic and physiological processes with the external signals. So, misalignment of environmental and endogenous circadian rhythms leads to disruption of biological activities in living organisms. Noncoding transcripts including antisense RNAs are an important component of the molecular clocks. Commonly, the antisense transcripts are involved in the regulation of gene expression. PER2AS and CRY1AS are the only known Natural Antisense Transcripts (NAT) among the core clock genes, which overlap with the PER2 and CRY1 genes, respectively. In this study, we hypothesized that PER2AS and CRY1AS like the other clock genes, exhibit the oscillatory behavior in a 24-hour period and affect the expression of PER2 and CRY1. First, the A549 cell line was cultured under standard conditions. After horse serum shock, RNA extraction and cDNA synthesis was performed; then the expression fluctuations of PER2AS, CRY1AS, PER2, and CRY1 were measured with Real-time PCR. Our result showed that PER2AS and CRY1AS had similar oscillation patterns with their sense strand during 24-hour period. Therefore, we suggested that PER2AS and CRY1AS transcripts probably by preventing the interaction of miRNAs with PER2 and CRY1 mRNAs, influence the expression of them, positively.

Highlights

The majority of living organisms are equipped with a time measuring system that is known as a circadian clock
The expression level of them varies at different time points but display similar oscillatory behavior with PER2 and CRY1 genes (Fig. 1). in addition, it seems that the circadian expression pattern of PER2 and CRY1 genes be in harmony with each other
Our results showed that PER2AS and CRY1AS as the sole antisense transcripts in the molecular clock genes, have a rhythmic expression pattern within 24 hours and the circadian fluctuation of them is similar to PER2 and CRY1 mRNAs, respectively

Summary

Introduction

The majority of living organisms are equipped with a time measuring system that is known as a circadian clock. The suprachiasmatic nucleus (SCN) as a master regulator of the mammalian circadian clock is responsible for synchronizing internal biological rhythms with day/night periods and controlling the peripheral clocks in the other tissues [1,2,3,4]. The primary feedback loop contains the core clock genes (CCG) including BMAL1, CLOCK, Period (PER1/2/3) and Cryptochrome (CRY1/2) family genes [8, 10]. BMAL1CLOCK heterodimer in a positive feedback loop, activate the expression of PER and CRY genes. The antisense transcripts are involved in the regulation of gene expression. PER2AS and CRY1AS are the only known Natural Antisense Transcripts (NAT) among the core clock genes, which overlap with the PER2 and CRY1 genes, respectively. We hypothesized that PER2AS and CRY1AS like the other clock genes, exhibit the oscillatory behavior in a 24-hour period and affect the expression of PER2 and CRY1. Conclusions: we suggested that PER2AS and CRY1AS transcripts probably by preventing the interaction of miRNAs with PER2 and CRY1 mRNAs, influence the expression of them, positively

Methods

Results

Conclusion