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 resistance to cisplatin-induced apoptosis. Knockdown of endogenous TERT Delta 2-4 in Calu-6 cells reduced clonogenicity and resistance to cisplatin. Our results suggest that TERT Delta 2-4 enhances cancer cells’ resistance to intrinsic apoptosis. RNA sequencing following knockdown of Delta 2-4 TERT indicates that translation is downregulated and that mitochondrial related proteins are upregulated compared to controls.
Kim, J.J., Ahn, A., Ying, J.Y. et al. Discovery and characterization of a novel telomerase alternative splicing isoform that protects lung cancer cells from chemotherapy induced cell death. Sci Rep 15, 6787 (2025). https://doi.org/10.1038/s41598-025-90639-3
