Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Oct 17;114(42):E8855-E8864. doi: 10.1073/pnas.1706611114. Epub 2017 Oct 2.

Period2 3'-UTR and microRNA-24 regulate circadian rhythms by repressing PERIOD2 protein accumulation.

Author information

1
Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX 77030; Seung-Hee.Yoo@uth.tmc.edu joseph.takahashi@utsouthwestern.edu.
2
Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390.
3
Department of Neurobiology, Northwestern University, Evanston, IL 60208.
4
Department of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
5
Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX 77030.
6
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235-1634.
7
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
8
Program in Neuroscience, Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306.
9
Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390; Seung-Hee.Yoo@uth.tmc.edu joseph.takahashi@utsouthwestern.edu.
10
Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390.

Abstract

We previously created two PER2::LUCIFERASE (PER2::LUC) circadian reporter knockin mice that differ only in the Per2 3'-UTR region: Per2::Luc, which retains the endogenous Per2 3'-UTR and Per2::LucSV, where the endogenous Per2 3'-UTR was replaced by an SV40 late poly(A) signal. To delineate the in vivo functions of Per2 3'-UTR, we analyzed circadian rhythms of Per2::LucSV mice. Interestingly, Per2::LucSV mice displayed more than threefold stronger amplitude in bioluminescence rhythms than Per2::Luc mice, and also exhibited lengthened free-running periods (∼24.0 h), greater phase delays following light pulse, and enhanced temperature compensation relative to Per2::Luc Analysis of the Per2 3'-UTR sequence revealed that miR-24, and to a lesser degree miR-30, suppressed PER2 protein translation, and the reversal of this inhibition in Per2::LucSV augmented PER2::LUC protein level and oscillatory amplitude. Interestingly, Bmal1 mRNA and protein oscillatory amplitude as well as CRY1 protein oscillation were increased in Per2::LucSV mice, suggesting rhythmic overexpression of PER2 enhances expression of Per2 and other core clock genes. Together, these studies provide important mechanistic insights into the regulatory roles of Per2 3'-UTR, miR-24, and PER2 in Per2 expression and core clock function.

KEYWORDS:

3′-UTR regulation; Per2 gene; circadian; miR-24; microRNA

PMID:
28973913
PMCID:
PMC5651750
DOI:
10.1073/pnas.1706611114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center