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NEAT1 modulates the TIRR/53BP1 complex to maintain genome integrity

Author

Listed:
  • Susan Kilgas

    (Harvard Medical School)

  • Aleem Syed

    (Harvard Medical School)

  • Patrick Toolan-Kerr

    (1 Midland Road
    5 Cutcombe Rd)

  • Michelle L. Swift

    (Harvard Medical School)

  • Shrabasti Roychoudhury

    (Harvard Medical School)

  • Aniruddha Sarkar

    (Harvard Medical School)

  • Sarah Wilkins

    (Harvard Medical School
    333 Cedar St)

  • Mikayla Quigley

    (Harvard Medical School
    300 Longwood Ave)

  • Anna R. Poetsch

    (Tatzberg 47-49)

  • Maria Victoria Botuyan

    (Mayo Clinic)

  • Gaofeng Cui

    (Mayo Clinic)

  • Georges Mer

    (Mayo Clinic)

  • Jernej Ule

    (1 Midland Road
    5 Cutcombe Rd)

  • Pascal Drané

    (Harvard Medical School)

  • Dipanjan Chowdhury

    (Harvard Medical School)

Abstract

Tudor Interacting Repair Regulator (TIRR) is an RNA-binding protein (RBP) that interacts directly with 53BP1, restricting its access to DNA double-strand breaks (DSBs) and its association with p53. We utilized iCLIP to identify RNAs that directly bind to TIRR within cells, identifying the long non-coding RNA NEAT1 as the primary RNA partner. The high affinity of TIRR for NEAT1 is due to prevalent G-rich motifs in the short isoform (NEAT1_1) region of NEAT1. This interaction destabilizes the TIRR/53BP1 complex, promoting 53BP1’s function. NEAT1_1 is enriched during the G1 phase of the cell cycle, thereby ensuring that TIRR-dependent inhibition of 53BP1’s function is cell cycle-dependent. TDP-43, an RBP that is implicated in neurodegenerative diseases, modulates the TIRR/53BP1 complex by promoting the production of the NEAT1 short isoform, NEAT1_1. Together, we infer that NEAT1_1, and factors regulating NEAT1_1, may impact 53BP1-dependent DNA repair processes, with implications for a spectrum of diseases.

Suggested Citation

  • Susan Kilgas & Aleem Syed & Patrick Toolan-Kerr & Michelle L. Swift & Shrabasti Roychoudhury & Aniruddha Sarkar & Sarah Wilkins & Mikayla Quigley & Anna R. Poetsch & Maria Victoria Botuyan & Gaofeng C, 2024. "NEAT1 modulates the TIRR/53BP1 complex to maintain genome integrity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52862-w
    DOI: 10.1038/s41467-024-52862-w
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    as
    1. Giulia Saredi & Hongda Huang & Colin M. Hammond & Constance Alabert & Simon Bekker-Jensen & Ignasi Forne & Nazaret Reverón-Gómez & Benjamin M. Foster & Lucie Mlejnkova & Till Bartke & Petr Cejka & Nie, 2016. "H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex," Nature, Nature, vol. 534(7609), pages 714-718, June.
    2. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    3. Oliver J. Ziff & Jacob Neeves & Jamie Mitchell & Giulia Tyzack & Carlos Martinez-Ruiz & Raphaelle Luisier & Anob M. Chakrabarti & Nicholas McGranahan & Kevin Litchfield & Simon J. Boulton & Ammar Al-C, 2023. "Integrated transcriptome landscape of ALS identifies genome instability linked to TDP-43 pathology," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Yaxin Dai & Aili Zhang & Shan Shan & Zihua Gong & Zheng Zhou, 2018. "Structural basis for recognition of 53BP1 tandem Tudor domain by TIRR," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    5. Jiaxu Wang & Zenglin Yuan & Yaqi Cui & Rong Xie & Guang Yang & Muzaffer A. Kassab & Mengxi Wang & Yinliang Ma & Chen Wu & Xiaochun Yu & Xiuhua Liu, 2018. "Molecular basis for the inhibition of the methyl-lysine binding function of 53BP1 by TIRR," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    6. Marie-Christine Caron & Ajit K. Sharma & Julia O’Sullivan & Logan R. Myler & Maria Tedim Ferreira & Amélie Rodrigue & Yan Coulombe & Chantal Ethier & Jean-Philippe Gagné & Marie-France Langelier & Joh, 2019. "Poly(ADP-ribose) polymerase-1 antagonizes DNA resection at double-strand breaks," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    7. Pascal Drané & Marie-Eve Brault & Gaofeng Cui & Khyati Meghani & Shweta Chaubey & Alexandre Detappe & Nishita Parnandi & Yizhou He & Xiao-Feng Zheng & Maria Victoria Botuyan & Alkmini Kalousi & Willia, 2017. "TIRR regulates 53BP1 by masking its histone methyl-lysine binding function," Nature, Nature, vol. 543(7644), pages 211-216, March.
    8. Hannah Farmer & Nuala McCabe & Christopher J. Lord & Andrew N. J. Tutt & Damian A. Johnson & Tobias B. Richardson & Manuela Santarosa & Krystyna J. Dillon & Ian Hickson & Charlotte Knights & Niall M. , 2005. "Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy," Nature, Nature, vol. 434(7035), pages 917-921, April.
    9. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
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