Regulation of human telomerase splicing by RNA:RNA pairing

Mandy S. Wong, Jerry W. Shay, Woodring E. Wright

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Article number3306
JournalNature communications
Volume5
DOIs
StatePublished - Feb 28 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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