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NONO, SFPQ, and PSPC1 promote telomerase recruitment to the telomere

Author

Listed:
  • Alexander P. Sobinoff

    (The University of Sydney)

  • Jadon K. Wells

    (The University of Sydney)

  • Maurice Chow

    (The University of Sydney)

  • Christopher B. Nelson

    (The University of Sydney)

  • Xinyi Wu

    (The University of Sydney)

  • Scott B. Cohen

    (The University of Sydney)

  • Yu Heng Lau

    (The University of Sydney)

  • Tracy M. Bryan

    (The University of Sydney)

  • Archa Fox

    (The University of Western Australia)

  • Hilda A. Pickett

    (The University of Sydney)

Abstract

Telomerase is a ribonucleoprotein enzyme that maintains telomeric repeats on chromosome ends in continuously dividing cells. Telomere maintenance via telomerase is dependent on the correct assembly of the enzyme complex, complex stabilization by associated cofactors, and effective recruitment to the telomere. Here, we show that telomerase is regulated in each of these processes by the Drosophila behaviour/human splicing (DBHS) family of RNA/DNA binding proteins (NONO, SFPQ and PSPC1). The DBHS proteins associate with catalytically active telomerase through the hTR RNA template component. Cells lacking the DBHS proteins display telomerase retention in nuclear Cajal bodies and impaired telomerase recruitment to the telomere, with NONO and PSPC1 depletion culminating in progressive telomere shortening in several cell lines, with the exception of long-term NONO depletion in 293 and 293T. Our results reveal the DBHS protein family as components of the telomerase trafficking machinery integral to telomere maintenance.

Suggested Citation

  • Alexander P. Sobinoff & Jadon K. Wells & Maurice Chow & Christopher B. Nelson & Xinyi Wu & Scott B. Cohen & Yu Heng Lau & Tracy M. Bryan & Archa Fox & Hilda A. Pickett, 2025. "NONO, SFPQ, and PSPC1 promote telomerase recruitment to the telomere," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60924-w
    DOI: 10.1038/s41467-025-60924-w
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    References listed on IDEAS

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    1. Eleonora Petti & Valentina Buemi & Antonina Zappone & Odessa Schillaci & Pamela Veneziano Broccia & Roberto Dinami & Silvia Matteoni & Roberta Benetti & Stefan Schoeftner, 2019. "SFPQ and NONO suppress RNA:DNA-hybrid-related telomere instability," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. João Vinagre & Ana Almeida & Helena Pópulo & Rui Batista & Joana Lyra & Vasco Pinto & Ricardo Coelho & Ricardo Celestino & Hugo Prazeres & Luis Lima & Miguel Melo & Adriana Gaspar da Rocha & Ana Preto, 2013. "Frequency of TERT promoter mutations in human cancers," Nature Communications, Nature, vol. 4(1), pages 1-6, October.
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