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

作者：Zhong, Fudi; Zhou, Nan; Wu, Kang; Guo, Yubiao; Tan, Weiping; Zhang, Hong; Zhang, Xue; Geng, Guannan; Pan, Ting; Luo, Haihua; Zhang, Yijun; Xu, Zhibin; Liu, Jun; Liu, Bingfeng; Gao, Wenchao; Liu, Chao; Ren, Liangliang; Li, Jun; Zhou, Jie; Zhang, Hui

来源：Nucleic Acids Research, 2015, 43(21): 10474-10491.

DOI：10.1093/nar/gkv954

• NOVO DNA METHYLATION
• PIWI PROTEINS
• DROSOPHILA-MELANOGASTER
• CHROMATIN STATE
• GENE-EXPRESSION
• MOUSE GERMLINE
• NONCODING RNA
• CANCER-CELLS
• 3' TERMINI
• IDENTIFICATION

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.

• 出版日期2015-12-2
• 单位中山大学