Zhao, K., Cheng, S., Miao, N., Xu, P., Lu, X., Zhang, Y., Wang, M., Ouyang, X., Yuan, X., Liu, W., Lu, X., Zhou, P., Gu, J., Zhang, Y., Qiu, D., Jin, Z., Su, C., Peng, C., Wang, J.H., Dong, M.Q., Wan, Y., Ma, J., Cheng, H., Huang, Y., Yu, Y. (2019). A Pandas complex adapted for piRNA-guided transcriptional silencing and heterochromatin formation.  Nat. Cell Biol. 21(10): 1261--1272.

FBrf0244040

Research paper

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.