Format

Send to

Choose Destination
Nat Commun. 2014 Feb 28;5:3306. doi: 10.1038/ncomms4306.

Regulation of human telomerase splicing by RNA:RNA pairing.

Author information

1
UT Southwestern Medical Center, Department of Cell Biology, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9039, USA.

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.

PMID:
24577044
PMCID:
PMC3948165
DOI:
10.1038/ncomms4306
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center