Circular RNA circZbtb20 maintains ILC3 homeostasis and function via Alkbh5-dependent m6A demethylation of Nr4a1 mRNA  

作　　者：Benyu Liu Nian Liu Xiaoxiao Zhu Liuliu Yang Buqing Ye Huimu Li Pingping Zhu Tiankun Lu Yong Tian Zusen Fan 

机构地区：[1]Key Laboratory of Infection and Immunity of CAS,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing,China [2]Research Center of Basic Medicine,Academy of Medical Sciences,Zhengzhou University,Zhengzhou,China [3]University of Chinese Academy of Sciences,Beijing,China [4]Key Laboratory of RNA Biology,Institute of Biophysics,Chinese Academy of Sciences,Beijing,China

出　　处：《Cellular & Molecular Immunology》2021年第6期1412-1424,共13页中国免疫学杂志（英文版）

基　　金：supported by the Ministry of Science and Technology of China(2020YFA0803501 and 2019YFA0508501);the National Natural Science Foundation of China⑶930036,81921003,92042302,31870883,91940305,31728006,81772646,and 31871494);the Strategic Priority Research Programs of the Chinese Academy of Sciences(XDB19030203);the Beijing Natural Science Foundation(5192018);the Biological Resource Program of the Chinese Academy of Science(KFJ-BRP-017-04);the Young Elite Scientist Sponsorship Program of CAST(2018QNRC001).

摘　　要：Group 3 innate lymphoid cells(ILC3s)play critical roles in innate immunity and gut homeostasis.However,how ILC3 homeostasis is regulated remains elusive.Here,we identified a novel circular RNA,circZbtb20,that is highly expressed in ILC3s and required for their maintenance and function.CircZbtb20 deletion causes reduced ILC3 numbers,increasing susceptibility to C.rodentium infection.Mechanistically,circZbtb20 enhances the interaction of Alkbh5 with Nr4a1 mRNA,leading to ablation of the m6A modification of Nr4a1 mRNA to promote its stability.Nr4a1 initiates Notch2 signaling activation,which contributes to the maintenance of ILC3 homeostasis.Deletion of Alkbh5 or Nr4a1 also impairs ILC3 homeostasis and increases susceptibilities to bacterial infection.Thus,our findings reveal an important role of circular RNA in the regulation of innate lymphoid cell homeostasis.

关 键 词：circZbtb20 ILC3 Alkbh5 Nr4a1 HOMEOSTASIS 

分 类 号：R392[医药卫生—免疫学]