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Mol Cell. 2003 May;11(5):1361-72.

Distinct biogenesis pathways for human telomerase RNA and H/ACA small nucleolar RNAs.

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1
Department of Molecular and Cell Biology, 401 Barker Hall, University of California at Berkeley, 97420, USA.

Abstract

Functional RNAs are processed according to cues from precursor expression context. The presence of an H/ACA motif within the human telomerase RNA (hTR) suggested that telomerase might utilize the biogenesis pathway of an H/ACA small nucleolar RNA. Here, we have investigated the requirements for processing, stability, and function of hTR. Instead of a biogenesis pathway dependent on transcription context or precursor sequence, we find that maturation of hTR requires cooperation of the H/ACA motif and an additional motif unique to the hTR H/ACA domain. This telomerase-specific hTR element is mutated in dyskeratosis congenita, and the disease-associated hTR substitution impairs RNA accumulation. Disease-associated hTR variants with sequence changes outside the H/ACA domain do not affect RNA processing or stability; they instead impose a catalytic defect. Our results reveal differences between the biogenesis of hTR and other H/ACA-motif RNAs and demonstrate distinct mechanisms of telomerase inhibition in human disease.

PMID:
12769858
DOI:
10.1016/s1097-2765(03)00196-5
[Indexed for MEDLINE]
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