A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production

TY - JOUR

T1 - A Heterochromatin-Specific RNA Export Pathway Facilitates piRNA Production

AU - ElMaghraby, Mostafa F

AU - Andersen, Peter Refsing

AU - Pühringer, Florian

AU - Hohmann, Ulrich

AU - Meixner, Katharina

AU - Lendl, Thomas

AU - Tirian, Laszlo

AU - Brennecke, Julius

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2019/8/8

Y1 - 2019/8/8

N2 - 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. Heterochromatic piRNA precursors escape classic mRNA quality-control and surveillance mechanisms through a dedicated nuclear export pathway.

AB - 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. Heterochromatic piRNA precursors escape classic mRNA quality-control and surveillance mechanisms through a dedicated nuclear export pathway.

KW - Crm1

KW - Drosophila germline

KW - NXF proteins

KW - RNA export

KW - RNA surveillance

KW - UAP56

KW - heterochromatin

KW - piRNA cluster

KW - piRNA pathway

KW - transposon control

UR - http://www.scopus.com/inward/record.url?scp=85070182912&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2019.07.007

DO - 10.1016/j.cell.2019.07.007

M3 - Journal article

C2 - 31398345

SN - 0092-8674

VL - 178

SP - 964

EP - 979

JO - Cell

JF - Cell

IS - 4

ER -