Mutations in many genes that control the expression, the function, or the stability of telomerase cause telomere biology disorders (TBDs), such as dyskeratosis congenita, pulmonary fibrosis, and aplastic anemia. Mutations in a subset of the genes associated with TBDs cause reductions of the telomerase RNA moiety hTR, thus limiting telomerase activity. We have recently found that loss of the trimethylguanosine synthase TGS1 increases both hTR abundance and telomerase activity and leads to telomere elongation. Here, we show that treatment with the S-adenosylmethionine analog sinefungin inhibits TGS1 activity, increases the hTR levels, and promotes telomere lengthening in different cell types. Our results hold promise for restoring telomere length in stem and progenitor cells from TBD patients with reduced hTR levels.

The S-adenosylmethionine analog sinefungin inhibits the trimethylguanosine synthase TGS1 to promote telomerase activity and telomere lengthening

Schoeftner S.
Membro del Collaboration Group
;
2022

Abstract

Mutations in many genes that control the expression, the function, or the stability of telomerase cause telomere biology disorders (TBDs), such as dyskeratosis congenita, pulmonary fibrosis, and aplastic anemia. Mutations in a subset of the genes associated with TBDs cause reductions of the telomerase RNA moiety hTR, thus limiting telomerase activity. We have recently found that loss of the trimethylguanosine synthase TGS1 increases both hTR abundance and telomerase activity and leads to telomere elongation. Here, we show that treatment with the S-adenosylmethionine analog sinefungin inhibits TGS1 activity, increases the hTR levels, and promotes telomere lengthening in different cell types. Our results hold promise for restoring telomere length in stem and progenitor cells from TBD patients with reduced hTR levels.
Pubblicato
https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.14240
File in questo prodotto:
File Dimensione Formato  
FEBS Letters - 2021 - Galati - The S‐adenosylmethionine analog sinefungin inhibits the trimethylguanosine synthase TGS1 to.pdf

accesso aperto

Tipologia: Documento in Versione Editoriale
Licenza: Creative commons
Dimensione 1.17 MB
Formato Adobe PDF
1.17 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/3014891
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 0
social impact