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L1 retrotransposons exploit RNA m6A modification as an evolutionary driving force

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Title
L1 retrotransposons exploit RNA m6A modification as an evolutionary driving force
Author(s)
Sung-Yeon Hwang; Jung, Hyunchul; Mun, Seyoung; Sungwon Lee; Kiwon Park; S. Chan Baek; Moon, Hyungseok C.; Hyewon Kim; Baekgyu Kim; Yongkuk Choi; Go, Young-Hyun; Tang, Wanxiangfu; Choi, Jongsu; Choi, Jung Kyoon; Cha, Hyuk-Jin; Park, Hye Yoon; Liang, Ping; V. Narry Kim; Han, Kyudong; Kwangseog Ahn
Publication Date
2021-02
Journal
Nature Communications, v.12, no.1
Publisher
Nature Research
Abstract
© 2021, The Author(s). 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.
URI
https://pr.ibs.re.kr/handle/8788114/9480
DOI
10.1038/s41467-021-21197-1
ISSN
2041-1723
Appears in Collections:
Center for RNA Research(RNA 연구단) > 1. Journal Papers (저널논문)
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