Ulaner G A, Hu J F, Vu T H, Giudice L C, Hoffman A R
Department of Gynecology & Obstetrics, Stanford University School of Medicine, Palo Alto, CA, USA.
Int J Cancer. 2001 Mar 1;91(5):644-9.
Direct genetic manipulations have shown that telomerase-mediated telomere elongation plays a key role in determining cellular replicative capacity and senescence. The mechanisms regulating the production of an active telomerase enzyme are still predominantly unknown, although roles for transcriptional control of hTERT, alternative-splicing of hTERT transcripts, and post-translational phosphorylation of hTERT protein have been advocated. Here we show that hTERT is alternatively spliced in specific patterns by different tissue types during human development. Alternative splicing often prohibits the expression of hTERT protein containing functional reverse transcriptase domains. In these instances, telomerase activity is absent, leading to shortening of telomeres. The specific pattern of hTERT mRNA variants in human development provides evidence that alternative splicing is non-random and participates in the regulation of telomerase activity.
直接的基因操作表明，端粒酶介导的端粒延长在决定细胞复制能力和衰老过程中起关键作用。尽管有人主张hTERT的转录控制、hTERT转录本的可变剪接以及hTERT蛋白的翻译后磷酸化发挥了作用，但调节活性端粒酶产生的机制仍主要未知。在这里，我们表明在人类发育过程中，hTERT在不同组织类型中以特定模式进行可变剪接。可变剪接通常会阻止含有功能性逆转录酶结构域的hTERT蛋白的表达。在这些情况下，端粒酶活性缺失，导致端粒缩短。人类发育过程中hTERT mRNA变体的特定模式提供了证据，表明可变剪接是非随机的，并参与端粒酶活性的调节。
