The Role of Alternative RNA Splicing in the Regulation of hTERT , Telomerase, and Telomeres: Implications for Cancer Therapeutics

Cancers
Aaron L SlusherAndrew T Ludlow

Abstract

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 a...Continue Reading

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Citations

May 1, 2021·Cancers·Mathushan SubasriDean H Betts
Sep 25, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Andreas M BeyerElizabeth R Jacobs
Jan 20, 2022·European Journal of Nuclear Medicine and Molecular Imaging·Liang ZhangDong Zhang

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Methods Mentioned

BETA
PCR
pulldown
antisense oligonucleotides
transfection
immunoprecipitation

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Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.