Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Cell Biol. 2019 Oct;21(10):1261-1272. doi: 10.1038/s41556-019-0396-0. Epub 2019 Sep 30.
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.
Piwi 相互作用 RNA（piRNA）途径对转座子的抑制对于保护动物生殖细胞至关重要。在果蝇中，Panoramix 通过与靶结合的 Piwi-piRNA 复合物结合来执行转录沉默，尽管这种情况的确切机制仍不清楚。在这里，我们表明 Panoramix 与核输出因子的生殖系特异性 paralogue dNxf2 及其辅助因子 dNxt1 (p15) 一起发挥作用，以抑制转座子的表达。转座子 RNA 结合蛋白 dNxf2 是动物生育力所必需的，并且是 Panoramix 介导的沉默所必需的。dNxf2 对新生转录本的瞬时束缚导致其在核内滞留。dNxf2 的 NTF2 结构域竞争性地将 dNxf1（TAP）从核孔蛋白上释放出来，这是正确的 RNA 输出所必需的。因此，dNxf2 在 Panoramix-dNxf2 依赖性 TAP/p15 沉默（Pandas）复合物中发挥作用，该复合物对抗典型的 RNA 输出机制，并将转座子限制在核周。我们的发现可能对理解 RNA 代谢如何调节异染色质形成具有更广泛的意义。
