Regulation of cell fate and gene silencing by liquid-liquid phase separation

René Ketting

The major focus of my lab is gene regulation by small RNAs. Small RNAs are regulatory non-coding RNAs that can have significant effects on translation, RNA stability and on chromatin. We use transgenics, genetics and biochemical and structural approaches to unravel the molecular pathways that are steered by small RNAs. We especially study embryogenesis and germ cell development, using C. elegans and zebrafish model systems.

We are currently working to understand how certain transcripts are selected to be turned into small regulatory RNAs, while others are not. This is crucial to understand, since these molecules fully set the target specificity of the regulatory processes. In addition, we work on understanding how small RNA pathways connect to other aspects of the cell's gene-regulatory programmes, including those active during germ cell specification and differentiation. Finally, an important current aim is to understand how phase separation acts to compartmentalise different steps in small RNA mediated gene regulation.

Research website

Positions held

  • Since 2022: Executive Director, Institute of Molecular Biology (IMB), Mainz
  • Since 2012: Scientific Director, IMB, Mainz; Professor, Faculty of Biology, Johannes Gutenberg University (JGU), Mainz
  • 2010 - 2013: Professor of Epigenetics in Development, University of Utrecht
  • 2005 - 2012: Group Leader, Hubrecht Institute, Utrecht
  • 2000 - 2004: Postdoctoral Researcher, Hubrecht Laboratory, Utrecht
  • 2000: Postdoctoral Researcher, Cold Spring Harbor Laboratories

Education

  • 2000: PhD in Molecular Biology, Netherlands Cancer Institute, Amsterdam
  • 1994: Masters in Chemistry, University of Leiden

Selected publications by René Ketting

Schreier J, Dietz S, Boermel M, Oorschot V, Seistrup AS, de Jesus Domingues AM, Bronkhorst AW, Nguyen DAH, Phillis S, Gleason EJ, L’Hernault SW, Phillips CM, Butter F and Ketting RF (2022) Membrane-associated cytoplasmic granules carrying the Argonaute protein WAGO-3 enable paternal epigenetic inheritance in Caenorhabditis elegans. Nat Cell Biol, 24:217–229 Link

Perez-Borrajero C, Podvalnaya N*, Holleis K*, Lichtenberger R, Karaulanov E, Simon B, Basquin J, Hennig J#, Ketting RF# and Falk S# (2021) Structural basis of PETISCO complex assembly during piRNA biogenesis in C. elegans. Genes Dev, 35:1304–1323 (*indicates joint contribution, #indicates joint correspondence) Link

Placentino M, de Jesus Domingues AM, Schreier J, Dietz S, Hellmann S, de Albuquerque BFM, Butter F and Ketting RF (2021) Intrinsically disordered protein PID-2 modulates Z granules and is required for heritable piRNA-induced silencing in the Caenorhabditis elegans embryo. EMBO J, 40:e105280 Link

Redl S*, de Jesus Domingues AM*, Caspani E, Möckel S, Salvenmoser W, Mendez-Lago M and Ketting RF (2021) Extensive nuclear gyration and pervasive non-genic transcription during primordial germ cell development in zebrafish. Development, 148:dev193060 (*indicates joint contribution) Link

Roovers EF, Kaaij LJT, Redl S, Bronkhorst AW, Wiebrands K, de Jesus Domingues AM, Huang HY, Han CT, Riemer S, Dosch R, Salvenmoser W, Grün D, Butter F, van Oudenaarden A and Ketting RF (2018) Tdrd6a regulates the aggregation of Buc into functional subcellular compartments that drive germ cell specification. Dev Cell, 46:285–301.e9 Link