title: Regulation of human telomerase splicing by RNA:RNA pairing.
abstract: Telomerase adds telomeric repeats onto chromosome ends and is almost universally upregulated in human cancers. Here we demonstrate that RNA:RNA pairing regulates splicing of the catalytic subunit of human telomerase (TERT). Human alleles contain a variable number of 38 bp repeats within TERT intron 6 (>1 kb from exon-intron junctions). At least nine repeats are required for generating the major non-functional 'minus beta' isoform, which skips exons 7 and 8. RNA:RNA pairing between the repeats and the pre-mRNA might bring exons 6 and 9 closer, thereby promoting exon skipping. To demonstrate this, we show that mutations within the repeat that abolish exon skipping are corrected by compensatory mutations in the pre-mRNA. This study thus identifies RNA:RNA pairing by repetitive sequences as a novel form of alternative splicing regulation in a gene crucial for cancer survival and sheds new light on functional roles for short repetitive sequences embedded deep within introns throughout the genome.
authors.affiliation: UT Southwestern Medical Center, Department of Cell Biology, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9039, USA.
authors.forename: Mandy S
authors.initials: MS
authors.lastname: Wong
authors.affiliation: UT Southwestern Medical Center, Department of Cell Biology, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9039, USA.
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Shay
authors.affiliation: UT Southwestern Medical Center, Department of Cell Biology, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9039, USA.
authors.forename: Woodring E
authors.initials: WE
authors.lastname: Wright
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D005091:Exons / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D009154:Mutation; D012326:RNA Splicing / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*
chemical_list: D019098:Telomerase