Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing

Kensaku Murano, Yuka Iwasaki, Hirotsugu Ishizu, Akane Mashiko, Aoi Shibuya, Shu Kondo, Shungo Adachi, Saori Suzuki, Kuniaki Saito, Tohru Natsume, Mikiko C. Siomi, Haruhiko Siomi

Research output: Contribution to journalArticle

Abstract

The PIWI-interacting RNA (piRNA) pathway preserves genomic integrity by repressing transposable elements (TEs) in animal germ cells. Among PIWI-clade proteins in Drosophila, Piwi transcriptionally silences its targets through interactions with cofactors, including Panoramix (Panx) and forms heterochromatin characterized by H3K9me3 and H1. Here, we identified Nxf2, a nuclear RNA export factor (NXF) variant, as a protein that forms complexes with Piwi, Panx, and p15. Panx–Nxf2–P15 complex formation is necessary in the silencing by stabilizing protein levels of Nxf2 and Panx. Notably, ectopic targeting of Nxf2 initiates co-transcriptional repression of the target reporter in a manner independent of H3K9me3 marks or H1. However, continuous silencing requires HP1a and H1. In addition, Nxf2 directly interacts with target TE transcripts in a Piwi-dependent manner. These findings suggest a model in which the Panx–Nxf2–P15 complex enforces the association of Piwi with target transcripts to trigger co-transcriptional repression, prior to heterochromatin formation in the nuclear piRNA pathway. Our results provide an unexpected connection between an NXF variant and small RNA-mediated co-transcriptional silencing.

Original languageEnglish
Article numbere102870
JournalEMBO Journal
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

Nuclear RNA
Cell Nucleus Active Transport
DNA Transposable Elements
Heterochromatin
RNA
Germ Cells
Animals
Proteins
Cells

Keywords

  • heterochromatin formation
  • nuclear RNA export factor
  • RNA silencing
  • transcriptional regulation
  • transposable element

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing. / Murano, Kensaku; Iwasaki, Yuka; Ishizu, Hirotsugu; Mashiko, Akane; Shibuya, Aoi; Kondo, Shu; Adachi, Shungo; Suzuki, Saori; Saito, Kuniaki; Natsume, Tohru; Siomi, Mikiko C.; Siomi, Haruhiko.

In: EMBO Journal, 01.01.2019.

Research output: Contribution to journalArticle

Murano, Kensaku ; Iwasaki, Yuka ; Ishizu, Hirotsugu ; Mashiko, Akane ; Shibuya, Aoi ; Kondo, Shu ; Adachi, Shungo ; Suzuki, Saori ; Saito, Kuniaki ; Natsume, Tohru ; Siomi, Mikiko C. ; Siomi, Haruhiko. / Nuclear RNA export factor variant initiates piRNA-guided co-transcriptional silencing. In: EMBO Journal. 2019.
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AU - Kondo, Shu

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