piRNA-independent transposon silencing by the Drosophila THO complex

Dev Cell. 2021 Sep 27;56(18):2623-2635.e5. doi: 10.1016/j.devcel.2021.08.021. Epub 2021 Sep 20.

Abstract

piRNAs guide Piwi/Panoramix-dependent H3K9me3 chromatin modification and transposon silencing during Drosophila germline development. The THO RNA export complex is composed of Hpr1, Tho2, and Thoc5-7. Null thoc7 mutations, which displace Thoc5 and Thoc6 from a Tho2-Hpr1 subcomplex, reduce expression of a subset of germline piRNAs and increase transposon expression, suggesting that THO silences transposons by promoting piRNA biogenesis. Here, we show that the thoc7-null mutant combination increases transposon transcription but does not reduce anti-sense piRNAs targeting half of the transcriptionally activated transposon families. These mutations also fail to reduce piRNA-guided H3K9me3 chromatin modification or block Panoramix-dependent silencing of a reporter transgene, and unspliced transposon transcripts co-precipitate with THO through a Piwi- and Panoramix-independent mechanism. Mutations in piwi also dominantly enhance germline defects associated with thoc7-null alleles. THO thus functions in a piRNA-independent transposon-silencing pathway, which acts cooperatively with Piwi to support germline development.

Keywords: H3K4me2; H3K9me3; Piwi; THO; Thoc7; germline development; piRNA; transcriptional silencing; transposon silencing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Cell Nucleus / metabolism
  • DNA Transposable Elements / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Silencing / physiology*
  • Germ Cells / metabolism
  • Nuclear Proteins / metabolism*
  • RNA, Small Interfering / genetics*

Substances

  • Argonaute Proteins
  • DNA Transposable Elements
  • Drosophila Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • THOC5 protein, Drosophila