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Regulation of human telomerase splicing by RNA:RNA pairing

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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)

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.

Suggested Citation

  • Mandy S. Wong & Jerry W. Shay & Woodring E. Wright, 2014. "Regulation of human telomerase splicing by RNA:RNA pairing," Nature Communications, Nature, vol. 5(1), pages 1-6, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4306
    DOI: 10.1038/ncomms4306
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