title: A SnoRNA-derived piRNA interacts with human interleukin-4 pre-mRNA and induces its decay in nuclear exosomes.
abstract: 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.
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Fudi
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Wu
authors.affiliation: Respiratory Division & Medicine Intensive Care Unit, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Yubiao
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pediatrics, the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Tan
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Geng
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Pan
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Luo
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Bingfeng
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Gao
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Ren
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Tropical Diseases Control of Ministry of Education of China, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China zhangh92@mail.sysu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D001249:Asthma / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D063326:Exosome Multienzyme Ribonuclease Complex / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D007438:Introns; D012322:RNA Precursors / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism*; D020537:RNA, Small Nucleolar / Q000737:chemistry; D018418:Th2 Cells / Q000276:immunology
chemical_list: C508598:IL4 protein, human; D012322:RNA Precursors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020537:RNA, Small Nucleolar; D015847:Interleukin-4; D063326:Exosome Multienzyme Ribonuclease Complex