An emerging consensus for telomerase RNA structure.

Abstract

Telomerase maintains telomere length by adding G-rich telomeric repeats to the ends of linear eukaryotic chromosomes. The core telomerase enzyme consists of two components: an essential RNA component and a catalytic protein component. The catalytic component, telomerase reverse transcriptase (TERT), contains sequence motifs homologous to those in the catalytic domain of reverse transcriptase enzymes. Although the TERT component of telomerase is fairly conserved among eukaryotes, the RNA component varies dramatically in sequence composition and in size. The structure of the telomerase RNA has been well established in ciliates and vertebrates (1–4). These structural models have led to experiments that provided fundamental insight into telomerase RNA function. However, it has been difficult to determine the global secondary structure of the very large yeast RNA. In the past month, there have been four new reports proposing a secondary structure for the yeast telomerase RNA (5–8). In this issue of PNAS, Blackburn and colleagues (7) propose a core structure for the yeast telomerase RNA that resembles the structure present in ciliate and vertebrate telomerase RNAs. Telomerase RNA is very divergent across eukaryotic species. The size ranges from ≈150 nt in ciliates to >1,300 nt in fungi. Although there is some sequence similarity within each group of closely related eukaryotes, there is no sequence similarity between groups. Thus, the telomerase RNA sequences from vertebrates cannot be aligned with the RNA sequences from ciliates. The rapid divergence in RNA size and sequence has made it difficult to identify common secondary structures for telomerase RNAs. Phylogenetic comparative analysis has proven to be the most powerful approach for inferring higher-order RNA structures. In this method, base paired helices in RNA secondary structure are determined by nucleotide covariation between species (9). For example, an A:U base pair in one species may change to a …