Comprehensive analysis of microRNA-mRNA co-expression in circadian rhythm

Young-Ji Na,Hee Sup Shin,Suk Chan Lee,Jung Hwan Sung,Ju Han Kim,Young-Ju Lee,Yeun Joo Choi,Woong-Yang Park

doi:10.3858/emm.2009.41.9.070

Abstract

To investigate the potential role of microRNA (miRNA) in the regulation of circadian rhythm, we performed microarray-based expression profiling study of both miRNA and mRNA in mouse liver for 48 h at 4-hour intervals. Circadian miRNA-mRNA target pair is defined as the pair both elements of which show circadian expression patterns and the sequence-based target relationship of which can be predicted. Circadian initiators, Clock and Bmal1, showed inversely correlated circadian expression patterns against their corresponding miRNAs, miR-181d and miR-191, targeting them. In contrast, circadian suppressors, Per, Cry, CKIe and Rev-erba, exhibited positively correlated circadian expression patterns to their corresponding miRNAs. Genomic location analysis revealed that intronic region showed higher abundance of cyclic than non-cyclic miRNAs targeting circadian genes while other (i.e., 3-UTR, exon and intergenic) regions showed no difference. It is suggested that miRNAs are involved in the regulation of peripheral circadian rhythm in mouse liver by modulating Clock:Bmal1 complex. Identifying specific miRNAs and their targets that are critically involved in circadian rhythm will provide a better understanding of the regulation of circadian- clock system.

Highlights

The circadian system in higher organisms temporally orchestrates rhythmic changes in a vast number of genes and gene products in different organs (Reppert and Weaver, 2001)
The present study showed the specific positive and negative correlation patterns of miRNA-mRNA target pairs in the circadian rhythm
Clock and Bmal1, which function as circadian transcription factors (Gekakis et al, 1998; Bunger et al, 2000), showed inversely correlated circadian expression patterns against their corresponding miRNAs, miR-181d and miR-191

Summary

Introduction

The circadian system in higher organisms temporally orchestrates rhythmic changes in a vast number of genes and gene products in different organs (Reppert and Weaver, 2001). MicroRNAs (miRNAs) are small, non-coding RNAs that act as potent silencers of gene expression (Lee et al, 1993; Pasquinelli et al, 2000; Lagos-Quintana et al, 2001; Lau et al, 2001; Lee and Ambros, 2001; Bartel, 2004). They recognize target mRNAs by base-pairing and thereby regulate their expression (Lewis et al, 2003; Kiriakidou et al, 2004). They are involved in various biological processes such as developmental timing and patterning, apoptosis, cell proliferation, organ development and tumorigenesis

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