Methylation of subtelomeric chromatin modifies the expression of the lncRNA TERRA, disturbing telomere homeostasis

Diego Oliva-Rico, Eunice Fabian-Morales, Rodrigo E. Cáceres-Gutiérrez, Adriana Gudiño, Fernanda Cisneros-Soberanis, Julieta Dominguez, Oscar Almaraz-Rojas, Cristian Arriaga-Canon, Clementina Castro-Hernández, Carlos De la Rosa, José L. Reyes, Luis A. Herrera*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The long noncoding RNA (lncRNA) telomeric repeat-containing RNA (TERRA) has been associated with telomeric homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, the impact of this association has not been investigated during the carcinogenic process. Determining whether changes in TERRA expression are a cause or a consequence of cell transformation is a complex task because studies are usually carried out using either cancerous cells or tumor samples. To determine the role of this lncRNA in cellular aging and chromosome healing, we evaluated telomeric integrity and TERRA expression during the establishment of a clone of untransformed myeloid cells. We found that reduced expression of TERRA disturbed the telomeric homeostasis of certain loci, but the expression of the lncRNA was affected only when the methylation of subtelomeric bivalent chromatin domains was compromised. We conclude that the disruption in TERRA homeostasis is a consequence of cellular transformation and that changes in its expression profile can lead to telomeric and genomic instability.

Original languageEnglish
Article number3271
Number of pages24
JournalInternational Journal of Molecular Sciences
Volume23
Issue number6
DOIs
Publication statusPublished - 18 Mar 2022

Keywords / Materials (for Non-textual outputs)

  • hTERT
  • LncRNA
  • telomeres
  • TERRA

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