Nature Genetics
27, 64 - 67 (2001)
doi:10.1038/83778
The function of a stem-loop in telomerase RNA is linked to the DNA repair
protein KuSuzanne E. Peterson1, Anne E. Stellwagen1, Scott J. Diede1, 2, Miriam S. Singer2, Zara W. Haimberger1, Catherine O. Johnson1, Monika Tzoneva3
& Daniel E. Gottschling1, 31
Division of Basic Sciences, Fred Hutchinson Cancer
Research Center, Seattle, Washington, USA.
2
The University of Chicago, Chicago,
Illinois, USA. 3
Department of Genetics, The University of Washington
, Seattle, Washington, USA.
Correspondence should be addressed to Daniel E. Gottschling dgottsch@fhcrc.orgThe telomerase enzyme lengthens telomeres, an activity essential for chromosome
stability in most eukaryotes. The enzyme is composed of a specialized reverse
transcriptase and a template RNA (ref. 1). In
Saccharomyces cerevisiae, overexpression of TLC1, the telomerase
RNA gene, disrupts telomeric structure2. The result is both
shortened telomere length and loss of a special chromatin structure that normally
silences telomere-proximal genes. Because telomerase function is not required
for telomeric silencing, we postulated that the dominant-negative effect caused
by overexpression of TLC1 RNA originates in a normal interaction between
the RNA and an unknown telomeric factor important for silencing; the overexpressed
RNA presumably continues to bind the factor and compromises its function3. Here we show that a 48-nt stem-loop structure within the 1.3-kb
TLC1 RNA is necessary and sufficient for disrupting telomeric silencing
and shortening telomeres. Moreover, this short RNA sequence appears to function
through an interaction with the conserved DNA end-binding protein Ku (ref. 4). We propose that, in addition to its roles in telomeric
silencing, homologous recombination and non-homologous end-joining (NHEJ),
S. cerevisiae Ku also helps to recruit or activate telomerase at the telomere
through an interaction with this stem-loop of TLC1 RNA.
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