| In order to adapt to the external environment,organisms evolve and adjust the physiological activities in the body to adapt to the cyclical changes with a period of approximately 24 hours-the circadian clock.The circadian clock enables organisms to anticipate and adapt to daily variations in environment.At the molecular level,the vertebrate circadian clock is based on the transcriptional/translational feedback loops of core clock genes.To maintain the daily rhythm icity,the circadian clock must synchronize rhythmic expressions of thousands of mRNAs and proteins with corresponding periods,phases and amplitudes,thus driving various rhythmic physiological activities.With the in-depth study of the genome,the post-transcriptional regulation of rhythmically expressed genes plays an important role in driving the rhythmic expression of mRNAs.With the development of sequencing technology,it is found that a large number of non-coding genes are also transcribed into RNAs.The previous studies have showed that these non-coding RNAs play important roles in the regulation of gene transcription and translation.Among them,microRNAs and long non-coding RNAs have attracted large attention since they were discovered in 1993 and 2009,respectively.MicroRNAs and long non-coding RNAs also are regulated by the circadian clock.The circadian clock regulates mRNAs at the transcriptional level,as well as microRNAs and lncRNAs,which do not encode proteins.These rhythmically expressed microRNAs and lncRNAs in turn regulate the expression of downstream genes at the pre-transcriptional,post-transcriptional and translational levels.Thus,we plan to investigate whether there is any network in which circadian clock-controlled microRNAs or lncRNAs regulate the rhythmic expression of downstream genes;and whether microRNAs or lncRNAs contribute to the post-transcriptional regulation of the circadian clock.Through bioinformatics analysis of high-throughput RNA sequencing data in zebrafish,we predicted three regulatory networks of microRNA-mRNA under circadian regulation:1)dre-miR-125b-1-3p and its target genes atp5j2 and calrl2;2)dre-miR-30e-5p and its target gene matn4;and 3)dre-miR-133a-3p and its target gene sdc2.We also predicted four LncRNA-mRNA regulatory networks under circadian regulation:1)LOC101882470 and calrl2,matn4;2)si:ch211-116o3.6 and atp5j2,sdc2;3)si:ch211-262n1.5 and calrl2,matn4;and 4)rars2 and calrl2,atp5j2,matn4 and sdc2.In this study,we examined the circadian clock-controlled networks of post-transcriptional regulation of downstream genes in zebrafish:the circadian clock not only indirectly regulates the rhythmic expression of atp5j2 and sdc2 through dre-miR-125b-1-3p and dre-miR-133a-3p;but also directly regulates the rhythmic expression of calrl2 and matn4 at the transcriptional level;and dre-miR-125b-1-3p and dre-miR-30e-5p in turn likely regulate the circadian clock at post-transcriptional level.We also found that the circadian clock regulates the expression of downstream genes through lncRNA:the circadian clock acts through si:ch211-116o3.6 to regulate the rhythmic expression of atp5j2 and sdc2;the circadian clock not only directly regulates the rhythmic expression of calrl2 and matn4 at the transcriptional level,but also regulates the post-transcriptional expression of calrl2 and matn4 via si:ch211-262n1.5.Take together,we elucidate the circadian clock-controlled networks of miRNA/lncRNA-mRNA in zebrafish,provide insights into the post-transcriptional regulation of the circadian clock,and facilitate functional investigation of miRNAs and lncRNAs in the circadian clock. |
