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Tytuł:
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mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence.
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Autorzy:
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Hwang SS; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Lim J; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Yu Z; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.; Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.; Yale Center for ImmunoMetabolism, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
Kong P; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Sefik E; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Xu H; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Harman CCD; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Kim LK; Severance Biomedical Science Institute and BK21 PLUS Project for Medical Sciences, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06230, Republic of Korea.
Lee GR; Department of Life Science, Sogang University, Seoul 04107, Republic of Korea.
Li HB; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.; Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.; Yale Center for ImmunoMetabolism, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
Flavell RA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA. .; Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA.
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Źródło:
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Science (New York, N.Y.) [Science] 2020 Mar 13; Vol. 367 (6483), pp. 1255-1260.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: : Washington, DC : American Association for the Advancement of Science
Original Publication: New York, N.Y. : [s.n.] 1880-
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MeSH Terms:
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Lymphocyte Activation*
RNA Stability*
Immediate-Early Proteins/*physiology
Neoplasm Proteins/*physiology
RNA, Messenger/*chemistry
T-Lymphocytes/*immunology
Tumor Suppressor Proteins/*physiology
Animals ; Cells, Cultured ; Immediate-Early Proteins/genetics ; Mice ; Mice, Knockout ; Neoplasm Proteins/genetics ; Polyadenylation ; Tumor Suppressor Proteins/genetics
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Grant Information:
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S10 OD018521 United States OD NIH HHS; United States HHMI Howard Hughes Medical Institute
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Substance Nomenclature:
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0 (Btg1 protein, mouse)
0 (Btg2 protein, mouse)
0 (Immediate-Early Proteins)
0 (Neoplasm Proteins)
0 (RNA, Messenger)
0 (Tumor Suppressor Proteins)
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Entry Date(s):
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Date Created: 20200314 Date Completed: 20200409 Latest Revision: 20200807
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Update Code:
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20240105
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DOI:
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10.1126/science.aax0194
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PMID:
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32165587
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T cells maintain a quiescent state prior to activation. As inappropriate T cell activation can cause disease, T cell quiescence must be preserved. Despite its importance, the mechanisms underlying the "quiescent state" remain elusive. Here, we identify BTG1 and BTG2 (BTG1/2) as factors responsible for T cell quiescence. BTG1/2-deficient T cells show an increased proliferation and spontaneous activation due to a global increase in messenger RNA (mRNA) abundance, which reduces the threshold to activation. BTG1/2 deficiency leads to an increase in polyadenylate tail length, resulting in a greater mRNA half-life. Thus, BTG1/2 promote the deadenylation and degradation of mRNA to secure T cell quiescence. Our study reveals a key mechanism underlying T cell quiescence and suggests that low mRNA abundance is a crucial feature for maintaining quiescence.
(Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
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