Alternative RNA splicing impacts the majority (>90%) of eukaryotic multi-exon genes, expanding the coding capacity and regulating the abundance of gene
isoforms.
Telomerase (hTERT) is a key example of a gene that is alternatively spliced during human fetal development and becomes dysregulated in nearly all
cancers. Approximately 90% of human
tumors use
telomerase to synthesize de novo telomere repeats and obtain telomere-dependent cellular immortality. Paradigm shifting data indicates that hTERT alternative splicing, in addition to transcription, plays an important role in the regulation of active
telomerase in cells. Our group and others are pursuing the basic science studies to progress this emerging area of
telomerase biology. Recent evidence demonstrates that switching splicing of hTERT from the
telomerase activity producing full-length hTERT
isoform to alternatively spliced, non-coding
isoforms may be a novel
telomerase inhibition strategy to prevent
cancer growth and survival. Thus, the goals of this review are to detail the general roles of
telomerase in
cancer development, explore the emerging regulatory mechanisms of alternative RNA splicing of the hTERT gene in various somatic and
cancer cell types, define the known and potential roles of hTERT splice
isoforms in
cancer cell biology, and provide insight into new treatment strategies targeting hTERT in
telomerase-positive
cancers.