Discovery and characterization of a novel telomerase alternative splicing isoform that protects lung cancer cells from chemotherapy induced cell death.

ABSTRACT: All cancer cells must adopt a telomere maintenance mechanism to achieve replicative immortality. Most human cancer cells utilize the enzyme telomerase to maintain telomeres. Alternative splicing of TERT regulates the amount and function of telomerase, however many alternative splicing isoforms of TERT have unknown functions. Single molecule long read RNA/cDNA sequencing of TERT revealed 45 TERT mRNA variants including 13 known and 32 novel variants. Among the variants, TERT Delta 2-4, which lacks exons 2-4 but retains the original open reading frame, was selected for further study. Induced pluripotent stem cells and cancer cells express higher levels of TERT Delta 2-4 compared to primary human bronchial epithelial cells. Overexpression of TERT Delta 2-4 enhanced clonogenicity and resistanc

SUBMITTER: Kim JJ 

PROVIDER: S-EPMC11861669 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature