IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42831-0.html
   My bibliography  Save this article

Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs

Author

Listed:
  • Ilaria Rosso

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Corey Jones-Weinert

    (IFOM ETS - The AIRC Institute of Molecular Oncology
    The Salk Institute for Biological Studies)

  • Francesca Rossiello

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Matteo Cabrini

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Silvia Brambillasca

    (IFOM ETS - The AIRC Institute of Molecular Oncology (Experimental Therapeutics Program))

  • Leonel Munoz-Sagredo

    (Karlsruhe Institute of Technology (KIT)
    Universidad de Valparaiso)

  • Zeno Lavagnino

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Emanuele Martini

    (IFOM ETS - The AIRC Institute of Molecular Oncology
    Università degli Studi di Milano)

  • Enzo Tedone

    (University of Texas Southwestern Medical Center)

  • Massimiliano Garre’

    (IFOM ETS - The AIRC Institute of Molecular Oncology
    RCSI, Royal College of Surgeons in Ireland, Department of Chemistry)

  • Julio Aguado

    (IFOM ETS - The AIRC Institute of Molecular Oncology
    The University of Queensland)

  • Dario Parazzoli

    (IFOM ETS - The AIRC Institute of Molecular Oncology)

  • Marina Mione

    (University of Trento)

  • Jerry W. Shay

    (University of Texas Southwestern Medical Center)

  • Ciro Mercurio

    (IFOM ETS - The AIRC Institute of Molecular Oncology (Experimental Therapeutics Program))

  • Fabrizio d’Adda di Fagagna

    (IFOM ETS - The AIRC Institute of Molecular Oncology
    Institute of Molecular Genetics IGM-CNR “Luigi Luca Cavalli-Sforza”)

Abstract

Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism activated in ~10–15% of cancers, characterized by telomeric damage. Telomeric damage-induced long non-coding RNAs (dilncRNAs) are transcribed at dysfunctional telomeres and contribute to telomeric DNA damage response (DDR) activation and repair. Here we observed that telomeric dilncRNAs are preferentially elevated in ALT cells. Inhibition of C-rich (teloC) dilncRNAs with antisense oligonucleotides leads to DNA replication stress responses, increased genomic instability, and apoptosis induction selectively in ALT cells. Cell death is dependent on DNA replication and is increased by DNA replication stress. Mechanistically, teloC dilncRNA inhibition reduces RAD51 and 53BP1 recruitment to telomeres, boosts the engagement of BIR machinery, and increases C-circles and telomeric sister chromatid exchanges, without increasing telomeric non-S phase synthesis. These results indicate that teloC dilncRNA is necessary for a coordinated recruitment of DDR factors to ALT telomeres and it is essential for ALT cancer cells survival.

Suggested Citation

  • Ilaria Rosso & Corey Jones-Weinert & Francesca Rossiello & Matteo Cabrini & Silvia Brambillasca & Leonel Munoz-Sagredo & Zeno Lavagnino & Emanuele Martini & Enzo Tedone & Massimiliano Garre’ & Julio A, 2023. "Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42831-0
    DOI: 10.1038/s41467-023-42831-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42831-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-42831-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Robert Lu & Julienne J. O’Rourke & Alexander P. Sobinoff & Joshua A. M. Allen & Christopher B. Nelson & Christopher G. Tomlinson & Michael Lee & Roger R. Reddel & Andrew J. Deans & Hilda A. Pickett, 2019. "The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT)," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Robert L. Dilley & Priyanka Verma & Nam Woo Cho & Harrison D. Winters & Anne R. Wondisford & Roger A. Greenberg, 2016. "Break-induced telomere synthesis underlies alternative telomere maintenance," Nature, Nature, vol. 539(7627), pages 54-58, November.
    3. Tsung-Po Lai & Ning Zhang & Jungsik Noh & Ilgen Mender & Enzo Tedone & Ejun Huang & Woodring E. Wright & Gaudenz Danuser & Jerry W. Shay, 2017. "A method for measuring the distribution of the shortest telomeres in cells and tissues," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    4. Bruno Silva & Rajika Arora & Silvia Bione & Claus M. Azzalin, 2021. "TERRA transcription destabilizes telomere integrity to initiate break-induced replication in human ALT cells," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    5. Sofia Francia & Flavia Michelini & Alka Saxena & Dave Tang & Michiel de Hoon & Viviana Anelli & Marina Mione & Piero Carninci & Fabrizio d’Adda di Fagagna, 2012. "Site-specific DICER and DROSHA RNA products control the DNA-damage response," Nature, Nature, vol. 488(7410), pages 231-235, August.
    6. Juan José Montero & Isabel López de Silanes & Osvaldo Graña & Maria A. Blasco, 2016. "Telomeric RNAs are essential to maintain telomeres," Nature Communications, Nature, vol. 7(1), pages 1-13, November.
    7. Hao Chen & Haibo Yang & Xiaolan Zhu & Tribhuwan Yadav & Jian Ouyang & Samuel S. Truesdell & Jun Tan & Yumin Wang & Meihan Duan & Leizhen Wei & Lee Zou & Arthur S. Levine & Shobha Vasudevan & Li Lan, 2020. "m5C modification of mRNA serves a DNA damage code to promote homologous recombination," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    8. Frances Karla Kusuma & Aishvaryaa Prabhu & Galen Tieo & Syed Moiz Ahmed & Pushkar Dakle & Wai Khang Yong & Elina Pathak & Vikas Madan & Yan Yi Jiang & Wai Leong Tam & Dennis Kappei & Peter Dröge & H. , 2023. "Signalling inhibition by ponatinib disrupts productive alternative lengthening of telomeres (ALT)," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Julio Aguado & Agustin Sola-Carvajal & Valeria Cancila & Gwladys Revêchon & Peh Fern Ong & Corey Winston Jones-Weinert & Emelie Wallén Arzt & Giovanna Lattanzi & Oliver Dreesen & Claudio Tripodo & Fra, 2019. "Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    10. Jennifer M. Mason & Yuen-Ling Chan & Ralph W. Weichselbaum & Douglas K. Bishop, 2019. "Non-enzymatic roles of human RAD51 at stalled replication forks," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    11. David Clynes & Clare Jelinska & Barbara Xella & Helena Ayyub & Caroline Scott & Matthew Mitson & Stephen Taylor & Douglas R. Higgs & Richard J. Gibbons, 2015. "Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    12. Stephen P. Jackson & Jiri Bartek, 2009. "The DNA-damage response in human biology and disease," Nature, Nature, vol. 461(7267), pages 1071-1078, October.
    13. Rajika Arora & Yongwoo Lee & Harry Wischnewski & Catherine M. Brun & Tobias Schwarz & Claus M. Azzalin, 2014. "RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    14. Bruno Silva & Richard Pentz & Ana Margarida Figueira & Rajika Arora & Yong Woo Lee & Charlotte Hodson & Harry Wischnewski & Andrew J. Deans & Claus M. Azzalin, 2019. "FANCM limits ALT activity by restricting telomeric replication stress induced by deregulated BLM and R-loops," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Chia-Yu Guh & Hong-Jhih Shen & Liv WeiChien Chen & Pei-Chen Chiu & I-Hsin Liao & Chen-Chia Lo & Yunfei Chen & Yu-Hung Hsieh & Ting-Chia Chang & Chien-Ping Yen & Yi-Yun Chen & Tom Wei-Wu Chen & Liuh-Yo, 2022. "XPF activates break-induced telomere synthesis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. S. Cohen & A. Guenolé & I. Lazar & A. Marnef & T. Clouaire & D. V. Vernekar & N. Puget & V. Rocher & C. Arnould & M. Aguirrebengoa & M. Genais & N. Firmin & R. A. Shamanna & R. Mourad & V. A. Bohr & V, 2022. "A POLD3/BLM dependent pathway handles DSBs in transcribed chromatin upon excessive RNA:DNA hybrid accumulation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Frances Karla Kusuma & Aishvaryaa Prabhu & Galen Tieo & Syed Moiz Ahmed & Pushkar Dakle & Wai Khang Yong & Elina Pathak & Vikas Madan & Yan Yi Jiang & Wai Leong Tam & Dennis Kappei & Peter Dröge & H. , 2023. "Signalling inhibition by ponatinib disrupts productive alternative lengthening of telomeres (ALT)," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Timothy K. Turkalo & Antonio Maffia & Johannes J. Schabort & Samuel G. Regalado & Mital Bhakta & Marco Blanchette & Diana C. J. Spierings & Peter M. Lansdorp & Dirk Hockemeyer, 2023. "A non-genetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Sile F. Yang & Christopher B. Nelson & Jadon K. Wells & Madushan Fernando & Robert Lu & Joshua A. M. Allen & Lisa Malloy & Noa Lamm & Vincent J. Murphy & Joel P. Mackay & Andrew J. Deans & Anthony J. , 2024. "ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Courtney A Lovejoy & Kaori Takai & Michael S Huh & David J Picketts & Titia de Lange, 2020. "ATRX affects the repair of telomeric DSBs by promoting cohesion and a DAXX-dependent activity," PLOS Biology, Public Library of Science, vol. 18(1), pages 1-28, January.
    7. Fei Li & Yizhe Wang & Inah Hwang & Ja-Young Jang & Libo Xu & Zhong Deng & Eun Young Yu & Yiming Cai & Caizhi Wu & Zhenbo Han & Yu-Han Huang & Xiangao Huang & Ling Zhang & Jun Yao & Neal F. Lue & Paul , 2023. "Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Valentina Buemi & Odessa Schillaci & Mariangela Santorsola & Deborah Bonazza & Pamela Veneziano Broccia & Annie Zappone & Cristina Bottin & Giulia Dell’Omo & Sylvie Kengne & Stefano Cacchione & Grazia, 2022. "TGS1 mediates 2,2,7-trimethyl guanosine capping of the human telomerase RNA to direct telomerase dependent telomere maintenance," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Meng Xu & Dulmi Senanayaka & Rongwei Zhao & Tafadzwa Chigumira & Astha Tripathi & Jason Tones & Rachel M. Lackner & Anne R. Wondisford & Laurel N. Moneysmith & Alexander Hirschi & Sara Craig & Sahar A, 2024. "TERRA-LSD1 phase separation promotes R-loop formation for telomere maintenance in ALT cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    10. Riham Smoom & Catherine Lee May & Vivian Ortiz & Mark Tigue & Hannah M. Kolev & Melissa Rowe & Yitzhak Reizel & Ashleigh Morgan & Nachshon Egyes & Dan Lichtental & Emmanuel Skordalakes & Klaus H. Kaes, 2023. "Telomouse—a mouse model with human-length telomeres generated by a single amino acid change in RTEL1," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    11. Halh Al-Serori & Franziska Ferk & Michael Kundi & Andrea Bileck & Christopher Gerner & Miroslav Mišík & Armen Nersesyan & Monika Waldherr & Manuel Murbach & Tamara T Lah & Christel Herold-Mende & Andr, 2018. "Mobile phone specific electromagnetic fields induce transient DNA damage and nucleotide excision repair in serum-deprived human glioblastoma cells," PLOS ONE, Public Library of Science, vol. 13(4), pages 1-17, April.
    12. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    13. Frederick Richards & Marta J. Llorca-Cardenosa & Jamie Langton & Sara C. Buch-Larsen & Noor F. Shamkhi & Abhishek Bharadwaj Sharma & Michael L. Nielsen & Nicholas D. Lakin, 2023. "Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    14. Junyeop Lee & Keewon Sung & So Young Joo & Jun-Hyeon Jeong & Seong Keun Kim & Hyunsook Lee, 2022. "Dynamic interaction of BRCA2 with telomeric G-quadruplexes underlies telomere replication homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    15. Jenny Kaur Singh & Rebecca Smith & Magdalena B. Rother & Anton J. L. Groot & Wouter W. Wiegant & Kees Vreeken & Ostiane D’Augustin & Robbert Q. Kim & Haibin Qian & Przemek M. Krawczyk & Román González, 2021. "Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    16. Miho M. Suzuki & Kenta Iijima & Koichi Ogami & Keiko Shinjo & Yoshiteru Murofushi & Jingqi Xie & Xuebing Wang & Yotaro Kitano & Akira Mamiya & Yuji Kibe & Tatsunori Nishimura & Fumiharu Ohka & Ryuta S, 2023. "TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    17. Ye Cai & Huifen Cao & Fang Wang & Yufei Zhang & Philipp Kapranov, 2022. "Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    18. Alyssa R Lindrose & Lauren W Y McLester-Davis & Renee I Tristano & Leila Kataria & Shahinaz M Gadalla & Dan T A Eisenberg & Simon Verhulst & Stacy Drury, 2021. "Method comparison studies of telomere length measurement using qPCR approaches: A critical appraisal of the literature," PLOS ONE, Public Library of Science, vol. 16(1), pages 1-23, January.
    19. Sidrah Shah & Alison Cheung & Mikolaj Kutka & Matin Sheriff & Stergios Boussios, 2022. "Epithelial Ovarian Cancer: Providing Evidence of Predisposition Genes," IJERPH, MDPI, vol. 19(13), pages 1-14, July.
    20. Jérémy Sandoz & Max Cigrang & Amélie Zachayus & Philippe Catez & Lise-Marie Donnio & Clèmence Elly & Jadwiga Nieminuszczy & Pietro Berico & Cathy Braun & Sergey Alekseev & Jean-Marc Egly & Wojciech Ni, 2023. "Active mRNA degradation by EXD2 nuclease elicits recovery of transcription after genotoxic stress," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42831-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.