由RNA調(diào)控的一些類型的沉默過程涉及次級(jí)siRNA的生成,,它們是通過將單鏈RNA轉(zhuǎn)變成雙鏈RNA生成的。這個(gè)過程是由一個(gè)“依賴于RNA的RNA聚合酶”( RdRP)完成的,。
現(xiàn)在,,Maida等人發(fā)現(xiàn),TERT(端粒酶的催化亞單元)可從線粒體“RNA處理核糖核酸內(nèi)切酶”(RMRP)的RNA部分生成dsRNA——以前的研究表明,,線粒體RMRP在“軟骨毛發(fā)發(fā)育不全”(一種遺傳性矮小癥)中發(fā)生突變,。所生成的dsRNA可被核糖核酸內(nèi)切酶“切片機(jī)”處理成siRNA。這是關(guān)于一種哺乳動(dòng)物RdRP活性的首次報(bào)告,。越來越多的證據(jù)表明,,TERT對(duì)細(xì)胞生理有所幫助,這種作用獨(dú)立于其使端粒伸長(zhǎng)的能力,,而這項(xiàng)新的研究工作則指出了其中所涉及的機(jī)制之一,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 461, 230-235 (10 September 2009) | doi:10.1038/nature08283
An RNA-dependent RNA polymerase formed by TERT and the RMRP RNA
Yoshiko Maida1, Mami Yasukawa1, Miho Furuuchi1, Timo Lassmann2, Richard Possemato3, Naoko Okamoto1, Vivi Kasim1, Yoshihide Hayashizaki2, William C. Hahn3,4 & Kenkichi Masutomi1,5
1 Cancer Stem Cell Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
2 RIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan
3 Department of Medical Oncology, Dana-Farber Cancer Institute and Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA
4 Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
5 PREST, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan
Correspondence to: William C. Hahn3,4Kenkichi Masutomi1,5 Correspondence and requests for materials should be addressed to W.C.H. or K.M.
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.