The function of TERRA in the regulation of telomerase in human cells is still debated. While TERRA interacts with telomerase, how it regulates telomerase function remains unknown. Here, we show that TERRA colocalizes with the telomerase RNA subunit hTR in the nucleoplasm and at telomeres during different phases of the cell cycle. We report that TERRA transcripts relocate away from chromosome ends during telomere lengthening, leading to a reduced number of telomeric TERRA-hTR molecules and consequent increase in "TERRA-free" telomerase molecules at telomeres. Using live-cell imaging and super-resolution microscopy, we show that upon transcription, TERRA relocates from its telomere of origin to long chromosome ends. Furthermore, TERRA depletion by antisense oligonucleotides promoted hTR localization to telomeres, leading to increased residence time and extended half-life of hTR molecules at telomeres. Overall, our findings indicate that telomeric TERRA transcripts inhibit telomere elongation by telomerase acting in trans, impairing telomerase access to telomeres that are different from their chromosome end of origin.

TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends / Bettin, Nicole; Querido, Emmanuelle; Gialdini, Irene; Grupelli, Glenda Paola; Goretti, Elena; Cantarelli, Marta; Andolfato, Marta; Soror, Eslam; Sontacchi, Alessandra; Jurikova, Katarina; Chartrand, Pascal; Cusanelli, Emilio. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 10:24(2024). [10.1126/sciadv.adk4387]

TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends

Bettin, Nicole
Primo
;
Grupelli, Glenda Paola;Goretti, Elena;Jurikova, Katarina;Cusanelli, Emilio
Ultimo
2024-01-01

Abstract

The function of TERRA in the regulation of telomerase in human cells is still debated. While TERRA interacts with telomerase, how it regulates telomerase function remains unknown. Here, we show that TERRA colocalizes with the telomerase RNA subunit hTR in the nucleoplasm and at telomeres during different phases of the cell cycle. We report that TERRA transcripts relocate away from chromosome ends during telomere lengthening, leading to a reduced number of telomeric TERRA-hTR molecules and consequent increase in "TERRA-free" telomerase molecules at telomeres. Using live-cell imaging and super-resolution microscopy, we show that upon transcription, TERRA relocates from its telomere of origin to long chromosome ends. Furthermore, TERRA depletion by antisense oligonucleotides promoted hTR localization to telomeres, leading to increased residence time and extended half-life of hTR molecules at telomeres. Overall, our findings indicate that telomeric TERRA transcripts inhibit telomere elongation by telomerase acting in trans, impairing telomerase access to telomeres that are different from their chromosome end of origin.
2024
24
Bettin, Nicole; Querido, Emmanuelle; Gialdini, Irene; Grupelli, Glenda Paola; Goretti, Elena; Cantarelli, Marta; Andolfato, Marta; Soror, Eslam; Sonta...espandi
TERRA transcripts localize at long telomeres to regulate telomerase access to chromosome ends / Bettin, Nicole; Querido, Emmanuelle; Gialdini, Irene; Grupelli, Glenda Paola; Goretti, Elena; Cantarelli, Marta; Andolfato, Marta; Soror, Eslam; Sontacchi, Alessandra; Jurikova, Katarina; Chartrand, Pascal; Cusanelli, Emilio. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 10:24(2024). [10.1126/sciadv.adk4387]
File in questo prodotto:
File Dimensione Formato  
Bettin_SciAdv_2024.pdf

accesso aperto

Tipologia: Versione editoriale (Publisher’s layout)
Licenza: Creative commons
Dimensione 7.46 MB
Formato Adobe PDF
7.46 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: https://hdl.handle.net/11572/413176
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact