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Nucleic Acids Res. 2015 Dec 2;43(21):10474-91. doi: 10.1093/nar/gkv954. Epub 2015 Sep 23.

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

Author information

1
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.
2
Respiratory Division & Medicine Intensive Care Unit, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
3
Department of Pediatrics, the Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510080, China.
4
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.

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.

PMID:
26405199
PMCID:
PMC4666397
DOI:
10.1093/nar/gkv954
[Indexed for MEDLINE]
Free PMC Article

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