The S-adenosylmethionine analog sinefungin inhibits the trimethylguanosine synthase TGS1 to promote telomerase activity and telomere lengthening
Authors
Alessandra Galati, Livia Scatolini, Emanuela Micheli, Francesca Bavasso, Alessandro Cicconi, Paolo Maccallini, Lu Chen, Caitlin M. Roake, Stefan Schoeftner, Steven E. Artandi, Maurizio Gatti, Stefano Cacchione, Grazia D. Raffa
Institution
Sapienza Universita di Roma
Country
Italy
Year
2021
Journal
FEBS Letters
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.