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 / Galati, A.; Scatolini, L.; Micheli, E.; Bavasso, F.; Cicconi, A.; Maccallini, P.; Chen, L.; Roake, C. M.; Schoeftner, S.; Artandi, S. E.; Gatti, M.; Cacchione, S.; Raffa, G. D.. - In: FEBS LETTERS. - ISSN 0014-5793. - 596:1(2022), pp. 42-52. [10.1002/1873-3468.14240]

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

Galati A.;Scatolini L.;Micheli E.;Bavasso F.;Maccallini P.;Gatti M.;Cacchione S.;Raffa G. D.
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.
2022
hTR; RNA methyltransferase; RNA processing; Sinefungin; telomerase; telomerase reverse transcriptase (TERT); telomere; telomere biology disorders (TBDs); telomere lengthening; TGS1
01 Pubblicazione su rivista::01a Articolo in rivista
The S-adenosylmethionine analog sinefungin inhibits the trimethylguanosine synthase TGS1 to promote telomerase activity and telomere lengthening / Galati, A.; Scatolini, L.; Micheli, E.; Bavasso, F.; Cicconi, A.; Maccallini, P.; Chen, L.; Roake, C. M.; Schoeftner, S.; Artandi, S. E.; Gatti, M.; Cacchione, S.; Raffa, G. D.. - In: FEBS LETTERS. - ISSN 0014-5793. - 596:1(2022), pp. 42-52. [10.1002/1873-3468.14240]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1599232
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