title: Oscillating primary transcripts harbor miRNAs with circadian functions.
abstract: The roles of miRNAs as important post-transcriptional regulators in the circadian clock have been suggested in several studies. But the search for circadian miRNAs has led to disparate results. Here we demonstrated that at least 57 miRNA primary transcripts are rhythmically transcribed in mouse liver. Most of these transcripts are under the regulation of circadian transcription factors such as BMAL1/CLOCK and REV-ERBα/β. However, the mature miRNAs derived from these transcripts are either not oscillating or oscillating at low amplitudes, which could explain the inconsistency of different circadian miRNA studies. In order to show that these circadian primary transcripts can give rise to miRNAs with circadian functions, we over-expressed one of them, miR-378, in mouse by adenovirus injection. We found a significant over-representation of circadian oscillating genes under-expressed by miR-378 over-expression in liver. In particular, we observed that miR-378 modulates the oscillation amplitudes of Cdkn1a in the control of cell cycle and Por in the regulation of oxidation reduction by forming partnership with different circadian transcription factors. Our study suggests that circadian transcription of miRNA at primary transcript level can be a good indicator for circadian miRNA functions.
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai 200031, China.|Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200031, China.
authors.forename: Haifang
authors.initials: H
authors.lastname: Wang
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai 200031, China.|University of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zenghua
authors.initials: Z
authors.lastname: Fan
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai 200031, China.|Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200031, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhao
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai 200031, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute for Biochemistry and Cell Biology, Shanghai 200031, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Lu
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.affiliation: Institute for Biochemistry and Cell Biology, Shanghai 200031, China.
authors.forename: Mofang
authors.initials: M
authors.lastname: Liu
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai 200031, China.|Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai 200031, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008099:Liver / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; C546119:MIRN378 microRNA, mouse; D035683:MicroRNAs; D003577:Cytochrome P-450 Enzyme System; D056926:CLOCK Proteins; C538944:Clock protein, mouse