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Tdrd1 acts as a molecular scaffold for Piwi proteins and piRNA targets in zebrafish

Hsin‐Yi Huang, Saskia Houwing, Lucas J T Kaaij, Amanda Meppelink, Stefan Redl, Sharon Gauci, Harmjan Vos, Bruce W Draper, Cecilia B Moens, Boudewijn M Burgering, Peter Ladurner, Jeroen Krijgsveld, Eugene Berezikov, René F Ketting

Author Affiliations

  1. Hsin‐Yi Huang1,
  2. Saskia Houwing1,§,
  3. Lucas J T Kaaij1,§,
  4. Amanda Meppelink1,
  5. Stefan Redl2,
  6. Sharon Gauci3,
  7. Harmjan Vos4,
  8. Bruce W Draper5,
  9. Cecilia B Moens6,
  10. Boudewijn M Burgering4,
  11. Peter Ladurner2,
  12. Jeroen Krijgsveld3,,
  13. Eugene Berezikov1 and
  14. René F Ketting*,1
  1. 1 Hubrecht Institute‐KNAW, University Medical Centre Utrecht, Utrecht, The Netherlands
  2. 2 Institute of Zoology, University of Innsbruck, Innsbruck, Austria
  3. 3 Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Centre for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences and Netherlands Proteomics Center, Utrecht University, Utrecht, The Netherlands
  4. 4 Department of Physiological Chemistry, University Medical Center Utrecht, Utrecht, The Netherlands
  5. 5 Molecular and Cellular Biology, University of California Davis, Davis, CA, USA
  6. 6 Howard Hughes Medical Institute and Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  1. *Corresponding author. Hubrecht Institute‐KNAW, University Medical Centre Utrecht, Uppsalalaan 8, Utrecht 3584 CT, The Netherlands. Tel.: +31 30 212 1800; Fax: +31 30 251 6554; E-mail: r.ketting{at}
  1. § These authors contributed equally to this work

  • Present address: Kimmel Center for Biology and Medicine at the Skirball Institute, NYU School of Medicine, 540 First Avenue, New York, NY 10016, USA

  • Present address: EMBL, Genome Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany

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Piwi proteins function in an RNAi‐like pathway that silences transposons. Piwi‐associated RNAs, also known as piRNAs, act as a guide to identify Piwi targets. The tudor domain‐containing protein Tdrd1 has been linked to this pathway but its function has thus far remained unclear. We show that zebrafish Tdrd1 is required for efficient Piwi‐pathway activity and proper nuage formation. Furthermore, we find that Tdrd1 binds both zebrafish Piwi proteins, Ziwi and Zili, and reveals sequence specificity in the interaction between Tdrd1 tudor domains and symmetrically dimethylated arginines (sDMAs) in Zili. Finally, we show that Tdrd1 complexes contain piRNAs and RNA molecules that are longer than piRNAs. We name these longer transcripts Tdrd1‐associated transcripts (TATs). TATs likely represent cleaved Piwi pathway targets and may serve as piRNA biogenesis intermediates. Altogether, our data suggest that Tdrd1 acts as a molecular scaffold for Piwi proteins, bound through specific tudor domain–sDMA interactions, piRNAs and piRNA targets.

  • Received April 13, 2011.
  • Accepted June 10, 2011.
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