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Mol Cell Biol. 2010 Sep;30(18):4368-78. doi: 10.1128/MCB.00384-10. Epub 2010 Jul 20.

Targeted 2'-O methylation at a nucleotide within the pseudoknot of telomerase RNA reduces telomerase activity in vivo.

Author information

  • 1Department of Biochemistry and Biophysics, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. yitao_yu@urmc.rochester.edu

Abstract

Telomerase RNA is an essential component of telomerase, a ribonucleoprotein enzyme that maintains chromosome ends in most eukaryotes. Here we employ a novel approach, namely, RNA-guided RNA modification, to assess whether introducing 2'-O methylation into telomerase RNA can influence telomerase activity in vivo. We generate specific 2'-O methylation sites in and adjacent to the triple helix (within the conserved pseudoknot structure) of Saccharomyces cerevisiae telomerase RNA (TLC1). We show that 2'-O methylation at U809 reduces telomerase activity, resulting in telomere shortening, whereas 2'-O methylation at A804 or A805 leads to moderate telomere lengthening. Importantly, we also show that targeted 2'-O methylation does not affect TLC1 levels and that 2'-O-methylated TLC1 appears to be efficiently assembled into telomerase ribonucleoprotein. Our results demonstrate that RNA-guided RNA modification is a highly useful approach for modulating telomerase activity.

PMID:
20647541
[PubMed - indexed for MEDLINE]
PMCID:
PMC2937528
Free PMC Article

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