Maida Yoshiko, Yasukawa Mami, Furuuchi Miho, Lassmann Timo, Possemato Richard, Okamoto Naoko, Kasim Vivi, Hayashizaki Yoshihide, Hahn William C, Masutomi Kenkichi
Cancer Stem Cell Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Nature. 2009 Sep 10;461(7261):230-5. doi: 10.1038/nature08283. Epub 2009 Aug 23.
Constitutive expression of telomerase in human cells prevents the onset of senescence and crisis by maintaining telomere homeostasis. However, accumulating evidence suggests that the human telomerase reverse transcriptase catalytic subunit (TERT) contributes to cell physiology independently of its ability to elongate telomeres. Here we show that TERT interacts with the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), a gene that is mutated in the inherited pleiotropic syndrome cartilage-hair hypoplasia. Human TERT and RMRP form a distinct ribonucleoprotein complex that has RNA-dependent RNA polymerase (RdRP) activity and produces double-stranded RNAs that can be processed into small interfering RNA in a Dicer (also known as DICER1)-dependent manner. These observations identify a mammalian RdRP composed of TERT in complex with RMRP.
人细胞中端粒酶的组成型表达通过维持端粒稳态来防止衰老和危机的发生。然而，越来越多的证据表明，人端粒酶逆转录酶催化亚基（TERT）对细胞生理的贡献与其延长端粒的能力无关。在此我们表明，TERT与线粒体RNA加工内切核糖核酸酶（RMRP）的RNA组分相互作用，RMRP是一种在遗传性多效综合征软骨毛发发育不全中发生突变的基因。人TERT和RMRP形成一种独特的核糖核蛋白复合体，该复合体具有RNA依赖性RNA聚合酶（RdRP）活性，并产生双链RNA，这些双链RNA可在Dicer（也称为DICER1）依赖性方式下被加工成小干扰RNA。这些观察结果鉴定出一种由TERT与RMRP形成复合体组成的哺乳动物RdRP。
