title: Alternative splicing regulation of telomerase: a new paradigm?
abstract: Alternative splicing affects approximately 95% of eukaryotic genes, greatly expanding the coding capacity of complex genomes. Although our understanding of alternative splicing has increased rapidly, current knowledge of splicing regulation has largely been derived from studies of highly expressed mRNAs. Telomerase is a key example of a protein that is alternatively spliced, but it is expressed at very low levels and although it is known that misregulation of telomerase splicing is a hallmark of nearly all cancers, the details of this process are unclear. Here we review work showing that hTERT expression is in part regulated by atypical alternative splicing, perhaps due to its exceptionally low expression level. We propose that these differential regulatory mechanisms may be widely applicable to other genes and may provide new opportunities for the development of cancer therapeutics.
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Mandy S
authors.initials: MS
authors.lastname: Wong
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
authors.affiliation: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75390-9039, USA; Center for Excellence in Genomics Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: jerry.shay@utsouthwestern.edu.
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D019098:Telomerase / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C491736:Dscam1 protein, Drosophila; C509186:TERT protein, human; D019098:Telomerase
keywords: RNA splicing; cancer therapy; low-abundance transcript; regulation; telomere