[논문]L1 retrotransposons exploit RNA m 6 A modification as an evolutionary driving force

Hwang, Sung-Yeon; Jung, Hyunchul; Mun, Seyoung; Lee, Sungwon; Park, Kiwon; Baek, S. Chan; Moon, Hyungseok C.; Kim, Hyewon; Kim, Baekgyu; Choi, Yongkuk; Go, Young-Hyun; Tang, Wanxiangfu; Choi, Jongsu; Choi, Jung Kyoon; Cha, Hyuk-Jin; Park, Hye Yoon; Liang, Ping; Kim, V. Narry; Han, Kyudong; Ahn, Kwangseog

doi:10.1038/s41467-021-21197-1

[해외논문] L1 retrotransposons exploit RNA m 6 A modification as an evolutionary driving force 원문보기

Nature communications, v.12 no.1, 2021년, pp.880 -

Hwang, Sung-Yeon (Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea) , Jung, Hyunchul (Department of Bio and Brain Engineering, KAIST, Daejeon, Republic of Korea) , Mun, Seyoung (Department of Nanobiomedical Science, Dankook University, Cheonan, Republic of Korea) , Lee, Sungwon (Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea) , Park, Kiwon (Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea) , Baek, S. Chan (Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea) , Moon, Hyungseok C. (Department of Physics and Astronomy, Seoul National University, Seoul, Republic of Korea) , Kim, Hyewon (Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea) , Kim, Baekgyu (Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea) , Choi, Yongkuk (Center for RNA Research, Institute for Basic Science, Seoul, Republic of Korea) , Go, Young-Hyun (Department of Pharmacy, Seoul National University, Seoul, Republic of Korea) , Tang, Wanxiangfu (Department of Biological Sciences, Brock University, St. Catharines, ON Canada) , Choi, Jongsu (Dr. von Hauner Chil) , Choi, Jung Kyoon , Cha, Hyuk-Jin , Park, Hye Yoon , Liang, Ping , Kim, V. Narry , Han, Kyudong , Ahn, Kwangseog

Abstract ▼ AI-Helper

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.L1 is a group of active retrotransposons in humans. Here the authors show that m6A modifications on L1 RNA increase translation efficiency and retrotransposition in human cells. M6A motifs are more enriched in evolutionary young L1s.

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