近日，奥地利科学院分子生物技术研究所Julius Brennecke和Peter Refsing Andersen研究组，合作报道了异染色质特异的RNA出核途径促进PIWI相互作用的RNA（piRNA）产生。2019年8月9日，国际知名学术期刊《细胞》发表了这一成果。

通过研究这些转录本如何实现出核，研究人员揭示了果蝇生殖系中piRNA前体特异性的RNA出核途径。该途径需要Nxf3-Nxt1，这是一个异源二聚mRNA出核受体Nxf1-Nxt1的变体。Nxf3与UAP56（一种对mRNA输出必需的核RNA解旋酶）以及CG13741 / Bootlegger相互作用，进而将Nxf3-Nxt1和UAP56募集到异染色的piRNA基因座。在与RNA货物结合后，Nxf3通过输出蛋白Crm1实现出核，并与Bootlegger一起累积在近核区域。这表明在出核后，Nxf3-Bootlegger将前体转录本运送至piRNA加工位点。这些发现表明，piRNA途径绕过核RNA监测系统，将未加工的转录本输出到细胞质中，这一策略也被逆转录病毒利用。

研究人员表示，piRNA指导动物的转座子沉默。22-30个核苷长度的piRNA在细胞质中由长的非编码RNA加工，而这些RNA通常缺乏出核转录本的RNA加工标志。

附：英文原文

Title: A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production

Author: Mostafa F. ElMaghraby, Peter Refsing Andersen, Florian Pühringer, Ulrich Hohmann, Katharina Meixner, Thomas Lendl, Laszlo Tirian, Julius Brennecke

Issue&Volume: Volume 178 Issue 4

Abstract: PIWI-interacting RNAs (piRNAs) guide transposon silencing in animals. The 22–30 nt piRNAs are processed in the cytoplasm from long non-coding RNAs that often lack RNA processing hallmarks of export-competent transcripts. By studying how these transcripts achieve nuclear export, we uncover an RNA export pathway specific for piRNA precursors in the Drosophila germline. This pathway requires Nxf3-Nxt1, a variant of the hetero-dimeric mRNA export receptor Nxf1-Nxt1. Nxf3 interacts with UAP56, a nuclear RNA helicase essential for mRNA export, and CG13741/Bootlegger, which recruits Nxf3-Nxt1 and UAP56 to heterochromatic piRNA source loci. Upon RNA cargo binding, Nxf3 achieves nuclear export via the exportin Crm1 and accumulates together with Bootlegger in peri-nuclear nuage, suggesting that after export, Nxf3-Bootlegger delivers precursor transcripts to the piRNA processing sites. These findings indicate that the piRNA pathway bypasses nuclear RNA surveillance systems to export unprocessed transcripts to the cytoplasm, a strategy also exploited by retroviruses.

DOI: https://doi.org/10.1016/j.cell.2019.07.007

Source：https://www.cell.com/cell/fulltext/S0092-8674(19)30772-X