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 und Ahn, Kwangseog (2021): L1 retrotransposons exploit RNA m(6)A modification as an evolutionary driving force. In: Nature Communications, Bd. 12, Nr. 1, 880

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 m(6)A modification. We discover that m(6)A 'writer' METTL3 facilitates L1 retrotransposition, whereas m(6)A 'eraser' ALKBH5 suppresses it. The essential m(6)A 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 m(6)A 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 m(6)A modification system for their successful replication. L1 is a group of active retrotransposons in humans. Here the authors show that m(6)A modifications on L1 RNA increase translation efficiency and retrotransposition in human cells. M(6)A motifs are more enriched in evolutionary young L1s.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch