Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b

Summary: Circadian rhythms regulate cell proliferation and differentiation; however, little is known about their roles in myogenic differentiation. Our synchronized differentiation studies demonstrate that myoblast proliferation and subsequent myotube formation by cell fusion occur in circadian mann...

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Main Authors: Matthew Lowe, Jacob Lage, Ellen Paatela, Dane Munson, Reilly Hostager, Ce Yuan, Nobuko Katoku-Kikyo, Mercedes Ruiz-Estevez, Yoko Asakura, James Staats, Mulan Qahar, Michaela Lohman, Atsushi Asakura, Nobuaki Kikyo
Format: Article
Language:English
Published: Elsevier 2018-02-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124718301414
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author Matthew Lowe
Jacob Lage
Ellen Paatela
Dane Munson
Reilly Hostager
Ce Yuan
Nobuko Katoku-Kikyo
Mercedes Ruiz-Estevez
Yoko Asakura
James Staats
Mulan Qahar
Michaela Lohman
Atsushi Asakura
Nobuaki Kikyo
author_facet Matthew Lowe
Jacob Lage
Ellen Paatela
Dane Munson
Reilly Hostager
Ce Yuan
Nobuko Katoku-Kikyo
Mercedes Ruiz-Estevez
Yoko Asakura
James Staats
Mulan Qahar
Michaela Lohman
Atsushi Asakura
Nobuaki Kikyo
author_sort Matthew Lowe
collection DOAJ
description Summary: Circadian rhythms regulate cell proliferation and differentiation; however, little is known about their roles in myogenic differentiation. Our synchronized differentiation studies demonstrate that myoblast proliferation and subsequent myotube formation by cell fusion occur in circadian manners. We found that one of the core regulators of circadian rhythms, Cry2, but not Cry1, is critical for the circadian patterns of these two critical steps in myogenic differentiation. This is achieved through the specific interaction between Cry2 and Bclaf1, which stabilizes mRNAs encoding cyclin D1, a G1/S phase transition regulator, and Tmem176b, a transmembrane regulator for myogenic cell fusion. Myoblasts lacking Cry2 display premature cell cycle exit and form short myotubes because of inefficient cell fusion. Consistently, muscle regeneration is impaired in Cry2−/− mice. Bclaf1 knockdown recapitulated the phenotypes of Cry2 knockdown: early cell cycle exit and inefficient cell fusion. This study uncovers a post-transcriptional regulation of myogenic differentiation by circadian rhythms.
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spelling doaj.art-83a1fd5ac5f940b095a88cb08937ef282022-12-22T01:45:18ZengElsevierCell Reports2211-12472018-02-012282118213210.1016/j.celrep.2018.01.077Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176bMatthew Lowe0Jacob Lage1Ellen Paatela2Dane Munson3Reilly Hostager4Ce Yuan5Nobuko Katoku-Kikyo6Mercedes Ruiz-Estevez7Yoko Asakura8James Staats9Mulan Qahar10Michaela Lohman11Atsushi Asakura12Nobuaki Kikyo13Stem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology, and Development , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology, and Development , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Bioinformatics and Computational Biology Graduate Program , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Department of Neurology , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology, and Development , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology, and Development , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology, and Development , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Department of Neurology , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USAStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Department of Neurology , University of Minnesota, Minneapolis, MN 55455, USA; Corresponding authorStem Cell Institute , University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology, and Development , University of Minnesota, Minneapolis, MN 55455, USA; Corresponding authorSummary: Circadian rhythms regulate cell proliferation and differentiation; however, little is known about their roles in myogenic differentiation. Our synchronized differentiation studies demonstrate that myoblast proliferation and subsequent myotube formation by cell fusion occur in circadian manners. We found that one of the core regulators of circadian rhythms, Cry2, but not Cry1, is critical for the circadian patterns of these two critical steps in myogenic differentiation. This is achieved through the specific interaction between Cry2 and Bclaf1, which stabilizes mRNAs encoding cyclin D1, a G1/S phase transition regulator, and Tmem176b, a transmembrane regulator for myogenic cell fusion. Myoblasts lacking Cry2 display premature cell cycle exit and form short myotubes because of inefficient cell fusion. Consistently, muscle regeneration is impaired in Cry2−/− mice. Bclaf1 knockdown recapitulated the phenotypes of Cry2 knockdown: early cell cycle exit and inefficient cell fusion. This study uncovers a post-transcriptional regulation of myogenic differentiation by circadian rhythms.http://www.sciencedirect.com/science/article/pii/S2211124718301414Bclaf1cell cyclecell fusioncircadian rhythmCry1Cry2
spellingShingle Matthew Lowe
Jacob Lage
Ellen Paatela
Dane Munson
Reilly Hostager
Ce Yuan
Nobuko Katoku-Kikyo
Mercedes Ruiz-Estevez
Yoko Asakura
James Staats
Mulan Qahar
Michaela Lohman
Atsushi Asakura
Nobuaki Kikyo
Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b
Cell Reports
Bclaf1
cell cycle
cell fusion
circadian rhythm
Cry1
Cry2
title Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b
title_full Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b
title_fullStr Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b
title_full_unstemmed Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b
title_short Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b
title_sort cry2 is critical for circadian regulation of myogenic differentiation by bclaf1 mediated mrna stabilization of cyclin d1 and tmem176b
topic Bclaf1
cell cycle
cell fusion
circadian rhythm
Cry1
Cry2
url http://www.sciencedirect.com/science/article/pii/S2211124718301414
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