Journal Article

A Pandas complex adapted for piRNA-guided transcriptional silencing and heterochromatin formation

Ma, Jinbiao, Cheng, Hong, Zhou, Peng, Wang, Ming, Liu, Weiwei, Wang, Jian-Hua, Yu, Yang, Yuan, Xun, Su, Chen, Huang, Ying, Zhao, Kang, Lu, Xiaohua, Zhang, Yuhan, Ouyang, Xuan, Wan, Youzhong, Zhang, Yiqun, Gu, Jiaqi, Miao, Na, Jin, Zhaohui, Cheng, Sha, Qiu, Ding, Peng, Chao, Lu, Xin, Dong, Meng-Qiu, Xu, Ping

2019

Overview

The repression of transposons by the Piwi-interacting RNA (piRNA) pathway is essential to protect animal germ cells. In Drosophila , Panoramix enforces transcriptional silencing by binding to the target-engaged Piwi–piRNA complex, although the precise mechanisms by which this occurs remain elusive. Here, we show that Panoramix functions together with a germline-specific paralogue of a nuclear export factor, dNxf2, and its cofactor dNxt1 (p15), to suppress transposon expression. The transposon RNA-binding protein dNxf2 is required for animal fertility and Panoramix-mediated silencing. Transient tethering of dNxf2 to nascent transcripts leads to their nuclear retention. The NTF2 domain of dNxf2 competes dNxf1 (TAP) off nucleoporins, a process required for proper RNA export. Thus, dNxf2 functions in a Panoramix–dNxf2-dependent TAP/p15 silencing (Pandas) complex that counteracts the canonical RNA exporting machinery and restricts transposons to the nuclear peripheries. Our findings may have broader implications for understanding how RNA metabolism modulates heterochromatin formation. Zhao et al. identify an unexpected role of the nuclear export factor Nxf2 as a partner of Panoramix in mediating piRNA-guided silencing. Nxf2 counteracts Nxf1-centred nuclear RNA transport to prevent the export of transposon transcripts.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 101/58 / 13/31 / 14/32 / 14/63 / 38 / 45/15 / 45/23 / 631/337/176/2016 / 631/337/384/2054 / 631/80/389 / 64/24 / 82/16 / 82/29 / Amino Acid Sequence / Animals / Animals, Genetically Modified / Argonaute Proteins - chemistry / Argonaute Proteins - genetics / Argonaute Proteins - metabolism / Binding proteins / Biomedical and Life Sciences / Cancer Research / Cell Biology / Cellular signal transduction / Chromatin / Chromatin Assembly and Disassembly / Developmental Biology / DNA Transposable Elements / Drosophila melanogaster - genetics / Drosophila melanogaster - growth & development / Drosophila melanogaster - metabolism / Drosophila Proteins - chemistry / Drosophila Proteins - genetics / Drosophila Proteins - metabolism / Exports / Female / Fertility / Fruit flies / Gene expression / Gene Expression Regulation, Developmental / Gene Silencing / Germ cells / Heterochromatin / Heterochromatin - metabolism / Heterochromatin - ultrastructure / Life Sciences / Models, Molecular / Nuclear Proteins - chemistry / Nuclear Proteins - genetics / Nuclear Proteins - metabolism / Nuclear transport / Nucleocytoplasmic Transport Proteins - chemistry / Nucleocytoplasmic Transport Proteins - genetics / Nucleocytoplasmic Transport Proteins - metabolism / Nucleoporins / Oocytes - metabolism / Oocytes - ultrastructure / Ovary - cytology / Ovary - metabolism / Protein Binding / Protein Interaction Domains and Motifs / Protein Structure, Secondary / Recombinant Proteins - chemistry / Recombinant Proteins - genetics / Recombinant Proteins - metabolism / RNA transport / RNA, Messenger - genetics / RNA, Messenger - metabolism / RNA, Small Interfering - genetics / RNA, Small Interfering - metabolism / RNA-binding protein / RNA-Binding Proteins - chemistry / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Sequence Alignment / Sequence Homology, Amino Acid / Stem Cells / Tethering / Transposons