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J Biol Chem. 2018 Jun 15;293(24):9140-9147. doi: 10.1074/jbc.AC118.003264. Epub 2018 May 7.

A critical role for nucleoporin 358 (Nup358) in transposon silencing and piRNA biogenesis in Drosophila.

Author information

1
From the Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425 and.
2
Yale Stem Cell Center and Department of Cell Biology, Yale University, New Haven, Connecticut 06510 haifan.lin@yale.edu.
3
From the Department of Biochemistry and Molecular Biology and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425 and gangaraj@musc.edu.

Abstract

Piwi-interacting RNAs (piRNAs) are a class of small noncoding RNAs that bind Piwi proteins to silence transposons and to regulate gene expression. In Drosophila germ cells, the Aubergine (Aub)-Argonaute 3 (Ago3)-dependent ping-pong cycle generates most germline piRNAs. Loading of antisense piRNAs amplified by this cycle enables Piwi to enter the nucleus and silence transposons. Nuclear localization is crucial for Piwi function in transposon silencing, but how this process is regulated remains unknown. It is also not known whether any of the components of the nuclear pore complex (NPC) directly function in the piRNA pathway. Here, we show that nucleoporin 358 (Nup358) and Piwi interact with each other and that a germline knockdown (GLKD) of Nup358 with short hairpin RNA prevents Piwi entry into the nucleus. The Nup358 GLKD also activated transposons, increased genomic instability, and derailed piRNA biogenesis because of a combination of decreased piRNA precursor transcription and a collapse of the ping-pong cycle. Our results point to a critical role for Nup358 in the piRNA pathway, laying the foundation for future studies to fully elucidate the mechanisms by which Nup358 contributes to piRNA biogenesis and transposon silencing.

KEYWORDS:

Nup358; Piwi; Piwi-interacting RNA; RAN-binding protein 2; RNA; RNA interference; RNAi; RanBP2; TE; nuclear pore; ovary; ping-pong cycle; transposable element

PMID:
29735528
PMCID:
PMC6005430
DOI:
10.1074/jbc.AC118.003264
[Indexed for MEDLINE]
Free PMC Article

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