한빛사논문
Sung-Yeon Hwang1,2, Hyunchul Jung3, Seyoung Mun4,5,6, Sungwon Lee1,2, Kiwon Park1,2, S. Chan Baek1,2, Hyungseok C. Moon7, Hyewon Kim1,2, Baekgyu Kim1,2, Yongkuk Choi1,2, Young-Hyun Go8, Wanxiangfu Tang9, Jongsu Choi10, Jung Kyoon Choi3, Hyuk-Jin Cha8, Hye Yoon Park7, Ping Liang9, V. Narry Kim1,2, Kyudong Han5,6,11,* & Kwangseog Ahn1,2,*
1Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea.
2School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
3Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea. 4Department of Nanobiomedical Science, Dankook University, Cheonan, Republic of Korea.
5DKU-Theragen institute for NGS analysis (DTiNa), Cheonan, Republic of Korea.
6Center for Bio Medical Engineering Core Facility, Dankook University, Cheonan, Republic of Korea.
7Department of Physics and Astronomy, Seoul National University, Seoul, Republic of Korea.
8Department of Pharmacy, Seoul National University, Seoul, Republic of Korea.
9Department of Biological Sciences, Brock University, St. Catharines, ON, Canada.
10Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany.
11Department of Microbiology, Dankook University, Cheonan, Republic of Korea.
*Corresponding author
Abstract
L1 retrotransposons can pose a threat to genome integrity. The host has evolved to restrict L1 replication. However, mechanisms underlying L1 propagation out of the host surveillance remains unclear. Here, we propose an evolutionary survival strategy of L1, which exploits RNA m6A modification. We discover that m6A ‘writer’ METTL3 facilitates L1 retrotransposition, whereas m6A ‘eraser’ ALKBH5 suppresses it. The essential m6A cluster that is located on L1 5′ UTR serves as a docking site for eukaryotic initiation factor 3 (eIF3), enhances translational efficiency and promotes the formation of L1 ribonucleoprotein. Furthermore, through the comparative analysis of human- and primate-specific L1 lineages, we find that the most functional m6A motif-containing L1s have been positively selected and became a distinctive feature of evolutionarily young L1s. Thus, our findings demonstrate that L1 retrotransposons hijack the RNA m6A modification system for their successful replication.
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