Telomerase RNA Structure and Function

Abstract

Telomeres, the specialized structures comprising the termini of eukaryotic chromosomes, are essential for stable chromosome maintenance and the complete replication of linear chromosomal DNA (for review, see Blackburn 1991; Zakian 1996). Telomeres appear to be involved in mitotic chromosomal maintenance as well as in processes occurring during critical developmental stages, such as premeiotic nuclear movement and interactions between homologous chromosomes (Chikashige et al. 1994; for review, see Blackburn 1994). In nearly all eukaryotes examined, the telomeric DNA consists of tracts of tandemly repeated sequences extending to the chromosomal ends. These telomeric repeats comprise the essential telomeric DNA sequences required for chromosomal stability and complete replication, and are generally short, G-rich tandem repeats on the strand running 5′ to 3′ toward the distal end of the chromosome. However, significant variations of this simple telomeric sequence motif have been found in some organisms (for review, see Blackburn 1994).

Cellular DNA polymerases can synthesize only in the 5′ to 3′ direction, requiring an RNA primer to initiate synthesis. Thus, the preservation of full-length linear chromosomal DNA requires a specialized cellular apparatus (Watson 1972). Without some form of terminal replicative mechanism, chromosomes would progressively recede from their ends, with loss of telomere-stabilizing functions, and ultimately, loss of essential coding regions. Telomerase, a ribonucleoprotein complex, is a unique cellular reverse transcriptase whose critical role in terminal chromosomal maintenance is to add telomeric sequence to the chromosomal DNA termini, and thereby compensate for incomplete replication. Telomerase activity has been detected in extracts from several diverse organisms...