UTR and Microrna-24 Regulate Circadian Rhythms By
Period2 3′-UTR and microRNA-24 regulate circadian PNAS PLUS rhythms by repressing PERIOD2 protein accumulation Seung-Hee Yooa,b,1, Shihoko Kojimab,2, Kazuhiro Shimomurac,3, Nobuya Koikeb,d, Ethan D. Buhrc,4, Tadashi Furukawac,5, Caroline H. Koc,6, Gabrielle Glostona, Christopher Ayouba, Kazunari Noharaa, Bryan A. Reyese, Yoshiki Tsuchiyad, Ook-Joon Yoof, Kazuhiro Yagitad, Choogon Leeg, Zheng Chena, Shin Yamazaki (山崎 晋)e,7, Carla B. Greenb, and Joseph S. Takahashib,h,1 aDepartment of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX 77030; bDepartment of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390; cDepartment of Neurobiology, Northwestern University, Evanston, IL 60208; dDepartment of Physiology and Systems Bioscience, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan; eDepartment of Biological Sciences, Vanderbilt University, Nashville, TN 37235-1634; fGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea; gProgram in Neuroscience, Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306; and hHoward Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, TX 75390 Contributed by Joseph S. Takahashi, September 7, 2017 (sent for review April 21, 2017; reviewed by Paul E. Hardin, Satchin Panda, and Hiroki R. Ueda) We previously created two PER2::LUCIFERASE (PER2::LUC) circadian for binding to the shared element RORE and thus play important reporter knockin mice that differ only in the Per2 3′-UTR region: Per2:: roles in circadian amplitude regulation (17). More recent studies Luc, which retains the endogenous Per2 3′-UTR and Per2::LucSV,where have also shown amplitude regulatory mechanisms distinct from the endogenous Per2 3′-UTR was replaced by an SV40 late poly(A) the competitive binding model (18, 19), suggesting an integrated signal.
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