Telomerase RNA TERC and the PI3K-AKT pathway form a positive feedback loop to regulate cell proliferation independent of telomerase activity.
Nucleic Acids Res
; 50(7): 3764-3776, 2022 04 22.
Article
em En
| MEDLINE
| ID: mdl-35323972
ABSTRACT
The core catalytic unit of telomerase comprises telomerase reverse transcriptase (TERT) and telomerase RNA (TERC). Unlike TERT, which is predominantly expressed in cancer and stem cells, TERC is ubiquitously expressed in normal somatic cells without telomerase activity. However, the functions of TERC in these telomerase-negative cells remain elusive. Here, we reported positive feedback regulation between TERC and the PI3K-AKT pathway that controlled cell proliferation independent of telomerase activity in human fibroblasts. Mechanistically, we revealed that TERC activated the transcription of target genes from the PI3K-AKT pathway, such as PDPK1, by targeting their promoters. Overexpression of PDPK1 partially rescued the deficiency of AKT activation caused by TERC depletion. Furthermore, we found that FOXO1, a transcription factor negatively regulated by the PI3K-AKT pathway, bound to TERC promoter and suppressed its expression. Intriguingly, TERC-induced activation of the PI3K-AKT pathway also played a critical role in the proliferation of activated CD4+ T cells. Collectively, our findings identify a novel function of TERC that regulates the PI3K-AKT pathway via positive feedback to elevate cell proliferation independent of telomerase activity and provide a potential strategy to promote CD4+ T cells expansion that is responsible for enhancing adaptive immune reactions to defend against pathogens and tumor cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA
/
Telomerase
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China