Related Experiment Video

Updated: Jun 16, 2025

Author Spotlight: Advanced Single-Molecule Techniques for Investigating Telomeric Protein-DNA Interactions
11:21

Author Spotlight: Advanced Single-Molecule Techniques for Investigating Telomeric Protein-DNA Interactions

Published on: August 30, 2024

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RIOK2 transcriptionally regulates TRiC and dyskerin complexes to prevent telomere shortening

Shrestha Ghosh1,2, Mileena T Nguyen3,4, Ha Eun Choi3

  • 1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Shrestha_Ghosh@dfci.harvard.edu.

Nature Communications
|August 20, 2024
PubMed

Insights

RIOK2 is identified as a key regulator of telomere maintenance, preventing shortening associated with aging, Myelodysplastic Syndromes (MDS), and Idiopathic Pulmonary Fibrosis (IPF). Restoring RIOK2 levels offers a potential therapeutic strategy for telomere disorders.

Area of Science:

  • Cell Biology
  • Genetics
  • Aging Research

Background:

  • Telomere shortening is a hallmark of aging and diseases like Myelodysplastic Syndromes (MDS) and Idiopathic Pulmonary Fibrosis (IPF).
  • The upstream regulation of telomerase, crucial for telomere maintenance, is not fully understood.
  • Telomerase activity prevents progressive telomere shortening, which can trigger DNA damage responses.

Purpose of the Study:

  • To identify novel regulators of telomere maintenance.
  • To elucidate the role of RIOK2 in telomere biology and its connection to aging and disease.
  • To explore RIOK2 as a potential therapeutic target for telomere shortening disorders.

Main Methods:

  • Identification of RIOK2 as a transcription factor regulating telomere maintenance.
  • Analysis of RIOK2's impact on TRiC and dyskerin complex subunit gene expression.
  • Assessment of RIOK2 expression levels in aged individuals, IPF patients, and MDS patient cells.
  • Evaluation of ectopic RIOK2 expression in primary lung fibroblasts from IPF patients.

Main Results:

  • RIOK2 acts as a critical transcription factor for telomere maintenance.
  • Loss of RIOK2 function downregulates key telomerase complex components, impairing telomerase activity and causing telomere shortening.
  • RIOK2 expression is reduced in aging, IPF, and correlates with telomere length in MDS.
  • Ectopic RIOK2 expression reverses telomere shortening in IPF-derived cells.

Conclusions:

  • RIOK2 is a crucial regulator of telomere length and telomerase activity.
  • Diminished RIOK2 contributes to telomere shortening in aging and related diseases.
  • Therapeutic strategies aimed at increasing RIOK2 levels may combat telomere shortening disorders.

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