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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.

SUBMITTER: Wong MS

PROVIDER: S-EPMC3948165 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Regulation of human telomerase splicing by RNA:RNA pairing.

Wong Mandy S MS Shay Jerry W JW Wright Woodring E WE

Nature communications 20140228

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 an ...[more]

PMID: 24577044

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