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Published September 30, 2023 | Version v1.1
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Non-catalytic function of PRC2 in the control of small RNA dynamics during programmed genome elimination in Paramecium

  • 1. Université Paris Cité, CNRS, Institut Jacques Monod, F-75013 Paris, France.
  • 2. Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette cedex, France

Description

To limit transposable element (TE) mobilization, most eukaryotes have evolved small RNAs to silence TE activity via homology-dependent mechanisms. Small RNAs, 20-30 nucleotides in length, bind to PIWI proteins and guide them to nascent transcripts by sequence complementarity, triggering the recruitment of histone methyltransferase enzymes on chromatin to repress the transcriptional activity of TEs and other repeats. In the ciliate Paramecium tetraurelia, 25-nt scnRNAs corresponding to TEs recruit Polycomb Repressive Complex 2 (PRC2), and trigger their elimination during the formation of the somatic nucleus. Here, we sequenced sRNAs during the entire sexual cycle with unprecedented precision. Our data confirmed that scnRNAs are produced from the entire germline genome, from TEs and non-TE sequences, during meiosis. Non-TE sRNAs are selectively degraded, which results in the specific selection of TE-scnRNAs.  We provide important mechanistic insight into the scnRNA selection pathway by identifying PRC2 and its cofactors as essential for the selective degradation of non-TE-scnRNAs. Our findings reveal a new mechanism for PRC2 that involves a non-methyltransferase function for regulating small RNA dynamics during development.

Notes

This work was supported by the Centre National de la Recherche Scientifique, the Agence Nationale pour la Recherche (ANR) [project "LaMarque" ANR-18-CE12-0005 to SD] and [project "POLYCHROME" ANR-19-CE12-0015 to SD and OA]; the LABEX Who Am I? to SD (ANR-11-LABX-0071; ANR-11-IDEX-0005-02); the Fondation de la Recherche Médicale "Equipe FRM EQU202203014643" to SD. CMP was recipient of PhD fellowships from Université Paris Cité and Fondation ARC, and a LABEX Who Am I? transition postdoc fellowship, OC was recipient of PhD fellowships from Université Paris Cité and Fondation de la Recherche Médicale and of a EUR GENE transition postdoc fellowship.

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Funding

Agence Nationale de la Recherche
LaMarque - Evolutionary transitions in genomic discrimination of self and non-self: small RNAs, sequence-specific factors and DNA methylation ANR-18-CE12-0005
Agence Nationale de la Recherche
POLYCHROME - Polycomb Repressive Complex in Paramecium: interaction with small RNA machinery and substrate specificity ANR-19-CE12-0015
Agence Nationale de la Recherche
WHO AM I - Determinants de l'Identité : de la molécule à l'individu ANR-11-LABX-0071