Identification and characterization of novel alternative splice variants in the 5' region of human TERT transcript in Jurkat cells
The human TERT gene, encoding the catalytic subunit of telomerase, is subject to extensive alternative splicing, which generates a variety of transcript isoforms with distinct or even opposing functions in telomere maintenance, cellular senescence, and cancer progression. However, the patterns of alternative splicing in the poorly characterized 5' region of the gene, specifically within exons 1-4 and the adjacent large intronic sequences, remain largely unexplored. The primary goal of this study was to comprehensively catalog and characterize novel splice variants occurring between exons 2 and 4 of the human TERT transcript in the Jurkat T-cell leukemia model using high-throughput next-generation sequencing. Our approach enabled the identification of 16 distinct splice variants, including 13 previously unreported isoforms, many of which arise from the activation of cryptic pseudoexons within intron 2. The relevance of this work lies in its contribution to a deeper understanding of the regulatory complexity of TERT expression. By revealing the diversity of aberrant splicing events in the 5' end of TERT, this study provides a foundation for future investigations into how non-canonical isoforms may influence telomerase-independent functions of TERT, contribute to splicing dysregulation in cancer, and potentially serve as biomarkers or therapeutic targets in malignancies.