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人端粒酶 RNA 成分的异位表达导致牛囊胚中端粒酶活性增加和端粒延长。

Ectopic expression of human telomerase RNA component results in increased telomerase activity and elongated telomeres in bovine blastocysts.

机构信息

Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Mariensee, Neustadt, Germany.

出版信息

Biol Reprod. 2012 Oct 25;87(4):95. doi: 10.1095/biolreprod.112.100198. Print 2012 Oct.

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.

摘要

端粒在衰老过程中起着重要作用,对哺乳动物细胞的再生能力至关重要。全酶端粒酶重建端粒,由两个组件组成,即催化蛋白端粒酶逆转录酶(TERT)和端粒酶 RNA(TERC)。TERC 在体细胞中广泛表达,被认为对端粒酶活性没有调节作用。在牛体细胞和胚胎细胞中转基因表达人端粒酶逆转录酶(hTERT)可延长端粒长度并增强端粒酶活性。为了更深入地了解这两个端粒酶成分的调节能力,我们研究了 hTERC 和 hTERT 增加牛胚胎中端粒酶活性和端粒长度的能力。分别将人 RNA 成分(hTERC)和/或人端粒酶的催化亚基(hTERT)的表达质粒注射到体外产生的牛受精卵的细胞质中。hTERC 的异位表达增加了牛囊胚中的端粒酶活性和端粒长度。与 hTERC 组相比,hTERT 和 hTERC 的共表达并没有导致端粒进一步延长。这些数据表明 TERC 是牛囊胚中端粒酶活性的限制因素之一,并进一步确立了牛着床前胚胎作为调节端粒长度的有用模型,对基础胚胎学和多能细胞的衍生具有重要影响。

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