Ectopic Expression of Human Telomerase RNA Component Results in Increased Telomerase Activity and Elongated Telomeres in Bovine Blastocysts1

Abstract

Telomeres play an important role in aging, and are critical for the regenerative capacity of mammalian cells. The holoenzyme telomerase rebuilds telomeres and is composed of two components, the catalytic protein telomerase reverse transcriptase (TERT) and the telomerase RNA (TERC). TERC is ubiquitously expressed in somatic cells and is thought to have no regulatory effects on telomerase activity. Transgenic expression of human TERT (hTERT) in bovine somatic and embryonic cells extends telomere length and enhances telomerase activity. To obtain further insight into the regulatory capacity of the two telomerase components, we have studied the ability of hTERC and hTERT to increase telomerase activity and telomere length in bovine embryos. Expression plasmids for the human RNA component (hTERC) and/or the catalytic subunit of human telomerase (hTERT), respectively, were injected into the cytoplasm of in vitro-produced bovine zygotes. Ectopic expression of hTERC increased telomerase activity and telomere length in bovine blastocysts. Coexpression of hTERT and hTERC did not result in further telomere elongation when compared to the hTERC group. These data indicate that TERC is one of the limiting factors of telomerase activity in bovine blastocysts, and further establish bovine preimplantation embryos as a useful model to modulate telomere length with impact for basic embryology and derivation of pluripotent cells.