15 Telomerase RNA

Abstract

According to the view of evolution in which genetic material was first in the form of RNA, a transition to the present-day DNA genomes occurred. In the current world, although most of the DNA genome of a eukaryote is replicated by copying of the preexisting parental DNA strands by DNA-dependent DNA polymerase, portions have also resulted from copying RNA into DNA. One of these genomic components is the telomeric DNA, which requires for its continued maintenance the action of a ribonucleoprotein (RNP) enzyme, telomerase.

Telomeres were originally defined functionally as the natural ends of eukaryotic chromosomes, without which a chromosome is unstable. Telomeric DNA in the form of very simple, tandemly repeated sequences is a conserved feature throughout nearly all the eukaryotes. A terminal stretch of this simple-sequence DNA, ranging in total length from under 50 bp in some ciliated protozoans, through a few hundred bp in yeasts and several other lower eukaryotes, to thousands of bp in mammalian cells, appears to supply sufficient cis-acting information to maintain a stable telomere. Examples of telomeric repeats are TTGGGG and TTAGGG repeats, found, respectively, in Tetrahymena thermophila, a ciliated protozoan, and in humans. Telomeric DNA sequences are usually such that they have a strand composition bias: At each chromosome end the strand containing the characteristic clusters of G residues (“G-strand”) runs 5′ to 3′ toward the chromosomal terminus.

The G-strand of telomeric DNA is synthesized in an unusual fashion by the ribonucleoprotein enzyme telomerase: As described below, a short RNA sequence within...