mRNA destabilization by BTG1 and BTG2 maintains T cell quiescence

Author:

Hwang Soo Seok1ORCID,Lim Jaechul1ORCID,Yu Zhibin123ORCID,Kong Philip1,Sefik Esen1,Xu Hao1,Harman Christian C. D.1,Kim Lark Kyun4ORCID,Lee Gap Ryol5ORCID,Li Hua-Bing123ORCID,Flavell Richard A.16ORCID

Affiliation:

1. Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.

2. Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.

3. Yale Center for ImmunoMetabolism, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China

4. Severance Biomedical Science Institute and BK21 PLUS Project for Medical Sciences, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06230, Republic of Korea.

5. Department of Life Science, Sogang University, Seoul 04107, Republic of Korea.

6. Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA.

Abstract

Deadenylate or activate? When cells are quiescent, they undergo reversible cell cycle arrest and evince low basal metabolism. Naïve T cells are normally quiescent until they recognize cognate antigens through T cell receptor–costimulatory molecule signaling. T cell quiescence appears to be an active process, but the mechanistic details are poorly understood. Hwang et al. report that the transcription factors BTG1 and BTG2 are selectively expressed in quiescent T cells. In mice, T cells conditionally knocked out for both factors showed enhanced proliferation and a lowered threshold of activation both in vitro and in response to Listeria monocytogenes infection. Deficiency of BTG1 and BTG2 resulted in increases in global messenger RNA half-life, suggesting that messenger RNA deadenylation and degradation are important processes for maintaining T cell quiescence. Science , this issue p. 1255

Funder

Howard Hughes Medical Institute

Jane Coffin Childs Memorial Fund for Medical Research

National Research Foundation of Korea

Leslie H. Warner Fellowship from Yale Cancer Center

HFSPO

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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