L1 retrotransposons exploit RNA m6A modification as an evolutionary driving force

Sung-Yeon Hwang, Hyunchul Jung, Seyoung Mun, Sungwon Lee, Kiwon Park, S. Chan Baek, Hyungseok C. Moon, Hyewon Kim, Baekgyu Kim, Yongkuk Choi, Young-Hyun Go, Wanxiangfu Tang, Jongsu Choi, Jung Kyoon Choi, Hyuk-Jin Cha, Hye Yoon Park, Ping Liang, V. Narry Kim, Kyudong Han () and Kwangseog Ahn ()
Additional contact information
Sung-Yeon Hwang: Center for RNA Research, Institute for Basic Science
Hyunchul Jung: KAIST
Seyoung Mun: Dankook University
Sungwon Lee: Center for RNA Research, Institute for Basic Science
Kiwon Park: Center for RNA Research, Institute for Basic Science
S. Chan Baek: Center for RNA Research, Institute for Basic Science
Hyungseok C. Moon: Seoul National University
Hyewon Kim: Center for RNA Research, Institute for Basic Science
Baekgyu Kim: Center for RNA Research, Institute for Basic Science
Yongkuk Choi: Center for RNA Research, Institute for Basic Science
Young-Hyun Go: Seoul National University
Wanxiangfu Tang: Brock University
Jongsu Choi: Ludwig-Maximilians-University of Munich
Jung Kyoon Choi: KAIST
Hyuk-Jin Cha: Seoul National University
Hye Yoon Park: Seoul National University
Ping Liang: Brock University
V. Narry Kim: Center for RNA Research, Institute for Basic Science
Kyudong Han: DKU-Theragen institute for NGS analysis (DTiNa)
Kwangseog Ahn: Center for RNA Research, Institute for Basic Science

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21197-1

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