Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase

查看全文 作　　者：Xiao-Li [1,8]Ping;Bao-Fa [1]Sun;Lu [2]Wang;Wen [1,8]Xiao;Xin [1]Yang;Wen-Jia [1]Wang;Samir [1]Adhikari;Yue [1]Shi;Ying [1]Lv;Yu-Sheng [1]Chen;Xu [1]Zhao;Ang [1]Li;Ying [1]Yang;Ujwal [1]Dahal;Xiao-Min [3]Lou;Xi [4]Liu;Jun [5]Huang;Wei-Ping [6]Yuan;Xiao-Fan [6]Zhu;Tao [6]Cheng;Yong-Liang [1]Zhao;Xinquan [4]Wang;Jannie M Rendtlew [1,7]Danielsen;Feng [2]Liu;Yun-Gui [1,8]Yang 机构地区：[1]Center For Genome Variations and Precision Bio-Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;[2]State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;[3]Chinese Academy of Sciences Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;[4]Center for Structural Biology, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;[5]Life Sciences Institute, Zhejiang University, Zhejiang 310058, China;[6]State Key Laboratory of Experimental Hematology, Institute of Hematology, Tianjin 300041, China;[7]The Novo Nordisk Foundation Center for Protein Research, Ubiquitin Signalling Group, Faculty of Health Sciences, Copenhagen, Denmark;[8]University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China 出　　处：《Cell Research》索引2014年第24卷第2期,共13页 基　　金：We thank Dr Chuan He for sharing his data before publishing, Drs Dang-Sheng Li and Guo-Liang Xu for their critical reading and suggestion. This work was supported by the National Basic Research Program of China (973 program; 2011CB510103 and 2012CB518302 to YGY, 2010CB945300 and 2011CB943900 to FL), the National Natural Science Foundation of China (31370796 and 91319308 to YGY, 30971678 to FL), 100 Talents Program of Chinese Academy of Sciences (CAS) (YGY), and CAS Strategic Priority Research Program (XDA01010110 to FL), SKLEH-Pilot Research Grant to YGY, and Danish Medical Research Council (JMRD). 摘　　要：包含 methyltransferase 建筑群的象 3 一样的 methyltransferase (METTL3 ) 催化 N6-methyladenosine (m6A ) 形成,一个新奇 epitranscriptomic 标记;然而,这建筑群的性质仍然保持大部分未知。这里,我们报导人的 m6A methyltransferase 建筑群, Wilm 的肿瘤 1 伙伴蛋白质(WTAP ) 和象 14 一样的 methyltransferase (METTL14 ) 的二个新部件。WTAP 与 METTL3 和 METTL14 交往,并且为他们的本地化被要求进在 vivo 与处理因素的 pre-mRNA 并且为 m6A methyltransferase 的催化活动充实的原子点缀。RNA 的多数在 vivo 由 WTAP 和 METTL3 跳了代表包含一致 m6A 主题的 mRNAs。当 WTAP 不在时, METTL3 的 RNA 有约束力的能力强烈被减少,建议 WTAP 可以工作调整到 mRNA 目标的 m6A methyltransferase 建筑群的招募。而且,在有 photoactivatable-ribonucleoside-enhanced crosslinking 和 immunoprecipitation (同等片断) 的联合的 transcriptomic 分析说明那 WTAP 和 METTL3 调整涉及抄写并且 RNA 处理的基因拼接的表示和选择。在 zebrafish 胚胎的调停 Morpholino 的击倒的指向 WTAP 或 METTL3 引起了织物区别缺点并且增加了 apoptosis。这些调查结果提供 WTAP 可以在 m6A methyltransferase 建筑群作为一个规章的子单元工作并且在 RNA 的 epitranscriptomic 规定起一个关键作用的充分证据新陈代谢。 关 键 词：RNA加工 哺乳动物 亚基 mRNA 肾母细胞瘤 选择性剪接 复合物 相关蛋白