Biochemistry

RNA Structure Conservation

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Science  17 Mar 2000:
Vol. 287, Issue 5460, pp. 1889
DOI: 10.1126/science.287.5460.1889a

Telomere length is maintained by the ribonucleoprotein enzyme telomerase, which contains a reverse transcriptase activity that adds sequence repeats onto the ends of chromosomes. These tandem repeats help to stabilize the double-stranded DNA ends of chromosomes.

Chen et al. construct a secondary structure model for the RNA component of vertebrate telomerase based on phylogenetic comparisons. To do this they cloned and sequenced 32 new telomerase RNA gene sequences from five different classes of vertebrates. Sequence alignment revealed eight conserved regions, and aligned sequences were analyzed for nucleotide covariation in order to identify residues likely to form double helical base pairs. One of the conserved regions is the template that specifies synthesis of the telomere repeats. Immediately adjacent is a domain predicted to adopt a pseudoknot structure. This pseudoknot region is known to be essential for activity of human telomerase, and another conserved secondary structure, the Box H/ACA domain, may contribute to RNA stability and nucleolar localization. The vertebrate structure has a similar overall topology to that of ciliate telomerase RNA despite extensive sequence divergence and evolutionary distance, suggesting that these structural motifs are critical for telomerase function.—VV

Cell100, 503 (2000).

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