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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.
