Huang C and Yu YT (2010) Targeted 2'-O Methylation at a Nucleotide within the Pseudoknot of Telomerase RNA Reduces Telomerase Activity In Vivo. Mol Cell Biol 30(18):4368-78
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 yeast 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.
|Status: Published||Type: Journal Article||PubMed ID: 20647541|
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