A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production
A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production
复制标题
异染色质特异的RNA输出途径促进piRNA的产生
DOI：
10.1016/j.cell.2019.07.007
复制
发表时间：
2019-08-08
期刊：
影响因子：
64.5
通讯作者：
Brennecke, Julius
中科院分区：
文献类型：
--
作者：
ElMaghraby, Mostafa F.;Andersen, Peter Refsing;Brennecke, Julius
PIWI相互作用RNA（piRNA）在动物中引导转座子沉默。22-30 nt piRNA在细胞质中由长的非编码RNA加工而成，所述长的非编码RNA通常缺乏具有输出能力的转录物的RNA加工标志。通过研究这些转录物如何实现核输出，我们发现了果蝇种系中皮尔纳前体特异性的RNA输出途径。这种途径需要Nxf 3-Nxt 1，一种异源二聚体mRNA输出受体Nxf 1-Nxt 1的变体。Nxf 3与mRNA输出所必需的核RNA解旋酶UAP 56和将Nxf 3-Nxt 1和UAP 56募集到异染色质皮尔纳源基因座的CG 13741/Bootlegger相互作用。在RNA货物结合后，Nxf 3通过输出蛋白Crm 1实现核输出，并与Bootlegger一起积累在核周核内，表明输出后，Nxf 3-Bootlegger将前体转录物递送到皮尔纳加工位点。这些发现表明，皮尔纳途径绕过核RNA监视系统，将未加工的转录物输出到细胞质中，这也是逆转录病毒利用的策略。
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.