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The S‐adenosylmethionine analog sinefungin inhibits the trimethylguanosine synthase TGS1 to promote telomerase activity and telomere lengthening
Author(s) -
Galati Alessandra,
Scatolini Livia,
Micheli Emanuela,
Bavasso Francesca,
Cicconi Alessandro,
Maccallini Paolo,
Chen Lu,
Roake Caitlin M.,
Schoeftner Stefan,
Artandi Steven E.,
Gatti Maurizio,
Cacchione Stefano,
Raffa Grazia D.
Publication year - 2022
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14240
Subject(s) - telomerase , telomere , dyskeratosis congenita , telomere binding protein , biology , telomerase rna component , cancer research , microbiology and biotechnology , telomerase reverse transcriptase , gene , genetics , dna binding protein , transcription factor
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.