Telomerase is a ribonucleoprotein enzyme that synthesises telomeric DNA repeats onto the ends of linear chromosomes, counteracting the progressive loss of telomere length that occurs through each cycle of DNA replication and cell division. Telomere shortening is a natural event of cellular ageing, wherein the reducing telomere length places limits on the number of times a cell can divide. In contrast, ~90% of cancers have activated telomerase to maintain stable telomere length, thereby conferring cellular immortality.
The telomerase enzyme complex consists of a catalytic reverse transcriptase protein component, a large multi-domain RNA component, and other associated proteins depending on the biological context and biochemical purification. Observed by electron microscopy, telomerase exists as an extended bilobal molecule – two dominant lobes connected through a narrow hinge. However, contrasting models for the molecular composition and architecture of the enzyme complex have been proposed; in each model it is the RNA component, with its conserved domains separated by extended flexible single-stranded regions, that serves as a scaffold to dictate the structure of the enzyme complex.
We present biochemical and structural observations supporting a functionally dimeric enzyme complex containing two catalytic centres. Furthermore, we show that the two catalytic lobes are held together through non-covalent bonding between two molecules of RNA. The broader implications of the RNA-RNA dimer interface and its conserved nature in RNA biology will be discussed.