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LARP3, LARP7, and MePCE are involved in the early stage of human telomerase RNA biogenesis

Author

Listed:
  • Tsai-Ling Kao

    (National Taiwan University)

  • Yu-Cheng Huang

    (National Taiwan University)

  • Yi-Hsuan Chen

    (National Taiwan University)

  • Peter Baumann

    (Johannes Gutenberg University
    Institute of Molecular Biology)

  • Chi-Kang Tseng

    (National Taiwan University)

Abstract

Human telomerase assembly is a highly dynamic process. Using biochemical approaches, we find that LARP3 and LARP7/MePCE are involved in the early stage of human telomerase RNA (hTR) and that their binding to RNA is destabilized when the mature form is produced. LARP3 plays a negative role in preventing the processing of the 3′-extended long (exL) form and the binding of LARP7 and MePCE. Interestingly, the tertiary structure of the exL form prevents LARP3 binding and facilitates hTR biogenesis. Furthermore, low levels of LARP3 promote hTR maturation, increase telomerase activity, and elongate telomeres. LARP7 and MePCE depletion inhibits the conversion of the 3′-extended short (exS) form into mature hTR and the cytoplasmic accumulation of hTR, resulting in telomere shortening. Taken together our data suggest that LARP3 and LARP7/MePCE mediate the processing of hTR precursors and regulate the production of functional telomerase.

Suggested Citation

  • Tsai-Ling Kao & Yu-Cheng Huang & Yi-Hsuan Chen & Peter Baumann & Chi-Kang Tseng, 2024. "LARP3, LARP7, and MePCE are involved in the early stage of human telomerase RNA biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50422-w
    DOI: 10.1038/s41467-024-50422-w
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    References listed on IDEAS

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    1. Chi-Kang Tseng & Hui-Fang Wang & Morgan R. Schroeder & Peter Baumann, 2018. "The H/ACA complex disrupts triplex in hTR precursor to permit processing by RRP6 and PARN," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Diego J. Páez-Moscoso & David V. Ho & Lili Pan & Katie Hildebrand & Kristi L. Jensen & Michaella J. Levy & Laurence Florens & Peter Baumann, 2022. "A putative cap binding protein and the methyl phosphate capping enzyme Bin3/MePCE function in telomerase biogenesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Jennifer Porat & Moaine El Baidouri & Jorg Grigull & Jean-Marc Deragon & Mark A. Bayfield, 2022. "The methyl phosphate capping enzyme Bmc1/Bin3 is a stable component of the fission yeast telomerase holoenzyme," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Laura C. Collopy & Tracy L. Ware & Tomas Goncalves & Sunnvør í Kongsstovu & Qian Yang & Hanna Amelina & Corinne Pinder & Ala Alenazi & Vera Moiseeva & Siân R. Pearson & Christine A. Armstrong & Kazuno, 2018. "LARP7 family proteins have conserved function in telomerase assembly," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
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