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Regulation of human telomerase splicing by RNA:RNA pairing

Mandy S. Wong, Jerry W. Shay and Woodring E. Wright ()
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Mandy S. Wong: UT Southwestern Medical Center, 5323 Harry Hines Boulevard
Jerry W. Shay: UT Southwestern Medical Center, 5323 Harry Hines Boulevard
Woodring E. Wright: UT Southwestern Medical Center, 5323 Harry Hines Boulevard

Nature Communications, 2014, vol. 5, issue 1, 1-6

Abstract: 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.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4306

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DOI: 10.1038/ncomms4306

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