2′-o methylation of internal adenosine by flavivirus ns5 methyltransferase2u2032- o甲基化黄病毒ns5内部腺苷的甲基转移酶.pdfVIP

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2′-o methylation of internal adenosine by flavivirus ns5 methyltransferase2u2032- o甲基化黄病毒ns5内部腺苷的甲基转移酶.pdf

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2′-o methylation of internal adenosine by flavivirus ns5 methyltransferase2u2032- o甲基化黄病毒ns5内部腺苷的甲基转移酶

29-O Methylation of Internal Adenosine by Flavivirus NS5 Methyltransferase 1,2 1 3 1 3 Hongping Dong , David C. Chang , Maggie Ho Chia Hua , Siew Pheng Lim , Yok Hian Chionh , 3 3 4 4 3,5 1,2 Fabian Hia , Yie Hou Lee , Petra Kukkaro , Shee-Mei Lok , Peter C. Dedon , Pei-Yong Shi * 1 Novartis Institute for Tropical Diseases, Singapore, 2 Wadsworth Center, New York State Department of Health, Albany, New York, United States of America, 3 Singapore- MIT Alliance for Research and Technology (SMART) Centre, Singapore, 4 Duke-NUS Graduate Medical School, Singapore, 5 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America Abstract RNA modification plays an important role in modulating host-pathogen interaction. Flavivirus NS5 protein encodes N-7 and 29-O methyltransferase activities that are required for the formation of 59 type I cap (m7GpppAm) of viral RNA genome. Here we reported, for the first time, that flavivirus NS5 has a novel internal RNA methylation activity. Recombinant NS5 proteins of West Nile virus and Dengue virus (serotype 4; DENV-4) specifically methylates polyA, but not polyG, polyC, or polyU, indicating that the methylation occurs at adenosine residue. RNAs with internal adenosines substituted with 29-O- methyladenosines are not active substrates for internal methylation, whereas RNAs with adenosines substituted with N6- methyladenosines can be efficiently methylated, suggesting that the internal methylation occurs