Forms and Functions of Telomerase RNA

Telomerase adds single-stranded telomeric DNA repeats to chromosome ends. Unlike other polymerases involved in genome replication, telomerase synthesizes DNA without use of a DNA template. Instead, the enzyme active site copies a template carried within the integral RNA subunit of the telomerase ribonucleoprotein (RNP) complex. In addition to providing a template, telomerase RNA has non-template motifs with critical functions in the catalytic cycle of repeat synthesis. In its complexity of structure and function, telomerase RNA resembles the noncoding RNAs of RNP machines like the ribosome and spliceosome that evolved from catalytic RNAs of the RNA World. However, unlike these RNPs, telomerase evolved its RNP identity after advent of the Protein World. Insights about telomerase have broad significance for understanding non-coding RNA biology as well as chromosome end maintenance and human disease. 14.1 Telomerase Biological Function and Regulation In all but few eukaryotes, nuclear chromosome ends terminate in a tandem array of simple-sequence repeats. Groups of eukaryotes have different sequences and lengths of telomeric repeat array, such as ∼1,000 repeats of T 2 AG 3 at an average human cell telomere or ∼50 repeats of T 2 G 4 at an average telomere in the single-celled model ciliate. The array of telomeric repeats serves at least two conserved functions (Gilson and Geli 2007; Verdun and Karlseder 2007). (1) telomeric repeats and their associated proteins form chromatin structures that protect authentic chromosome termini from fusion or degradation. (2) telomeric repeats provide a mechanism for telomere maintenance that can compensate for incomplete terminus replication by DNA-templated DNA polymerases. K. Collins Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720-3200, USA e-mail: [email protected]