A SnoRNA-derived piRNA interacts with human interleukin-4 pre-mRNA and induces its decay in nuclear exosomes

被引:114
作者
Zhong, Fudi [1 ,2 ,3 ]
Zhou, Nan [1 ,2 ,3 ]
Wu, Kang [1 ,2 ,3 ]
Guo, Yubiao [4 ,5 ]
Tan, Weiping [6 ]
Zhang, Hong [1 ,2 ,3 ]
Zhang, Xue [1 ,2 ,3 ]
Geng, Guannan [1 ,2 ,3 ]
Pan, Ting [1 ,2 ,3 ]
Luo, Haihua [1 ,2 ,3 ]
Zhang, Yijun [1 ,2 ,3 ]
Xu, Zhibin [1 ,2 ,3 ]
Liu, Jun [1 ,2 ,3 ]
Liu, Bingfeng [1 ,2 ,3 ]
Gao, Wenchao [1 ,2 ,3 ]
Liu, Chao [1 ,2 ,3 ]
Ren, Liangliang [1 ,2 ,3 ]
Li, Jun [1 ,2 ,3 ]
Zhou, Jie [1 ,2 ,3 ]
Zhang, Hui [1 ,2 ,3 ]
机构
[1] Sun Yat Sen Univ, Zhongshan Sch Med, Inst Human Virol, Guangzhou 510080, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Zhongshan Sch Med, Key Lab Trop Dis Control, Minist Educ China, Guangzhou 510080, Guangdong, Peoples R China
[3] Sun Yat Sen Univ, Zhongshan Sch Med, Guangdong Engn Res Ctr Antimicrobial Agent & Immu, Guangzhou 510080, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 1, Div Resp, Guangzhou 510080, Guangdong, Peoples R China
[5] Sun Yat Sen Univ, Affiliated Hosp 1, Med Intens Care Unit, Guangzhou 510080, Guangdong, Peoples R China
[6] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Pediat, Guangzhou 510080, Guangdong, Peoples R China
关键词
NOVO DNA METHYLATION; PIWI PROTEINS; DROSOPHILA-MELANOGASTER; CHROMATIN STATE; GENE-EXPRESSION; MOUSE GERMLINE; NONCODING RNA; CANCER-CELLS; 3' TERMINI; IDENTIFICATION;
D O I
10.1093/nar/gkv954
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
PIWI interacting RNAs (piRNAs) are highly expressed in germline cells and are involved in maintaining genome integrity by silencing transposons. These are also involved in DNA/histone methylation and gene expression regulation in somatic cells of invertebrates. The functions of piRNAs in somatic cells of vertebrates, however, remain elusive. We found that snoRNA-derived and C (C')/D' (D)-box conserved piRNAs are abundant in human CD4 primary T-lymphocytes. piRNA (piR30840) significantly downregulated interleukin-4 (IL-4) via sequence complementarity binding to pre-mRNA intron, which subsequently inhibited the development of Th2 T-lymphocytes. Piwil4 and Ago4 are associated with this piRNA, and this complex further interacts with Trf4-Air2-Mtr4 Polyadenylation (TRAMP) complex, which leads to the decay of targeted pre-mRNA through nuclear exosomes. Taken together, we demonstrate a novel piRNA mechanism in regulating gene expression in highly differentiated somatic cells and a possible novel target for allergy therapeutics.
引用
收藏
页码:10474 / 10491
页数:18
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