Modulation of circRNA Metabolism by m6A Modification
Copyright policy )Modulation of circRNA Metabolism by m6A Modification
N6-methyladenosine (m6A) is an RNA modification well-known for its contribution to different processes controlling RNA metabolism, including splicing, stability, and translation of mRNA. Conversely, the role of m6A on the biogenesis and function of circular RNAs (circRNAs) has yet to be addressed. circRNAs belong to a class of covalently closed transcripts produced via a back-splicing reaction whereby a downstream 5' splice donor site fuses to an upstream 3' splice acceptor site. Starting from circ-ZNF609 as a study case, we discover that specific m6As control its accumulation and that METTL3 and YTHDC1 are required to direct the back-splicing reaction. This feature is shared with other circRNAs because we find a significant direct correlation among METTL3 requirement, YTHDC1 binding, and the ability of m6A exons to undergo back-splicing. Finally, because circ-ZNF609 displays the ability to be translated, we show that m6A modifications, through recognition by YTHDF3 and eIF4G2, modulate its translation.
- University of Perugia Italy
- University of Groningen Netherlands
- University of Turin Italy
- Italian Institute of Technology Italy
- Roma Tre University Italy
Male, Adenosine, BIOGENESIS, Nerve Tissue Proteins, Methyltransferases, RNA, Circular, M6A, Alternative Splicing, HEK293 Cells, Child, Preschool, Humans, Female, RNA Splicing Factors, back-splicing; cap-independent translation; circRNA; circRNA biogenesis; circRNA translation; epitrascriptome; m; 6; A modification; METTL3; YTHDC1, TRANSLATION, MESSENGER-RNA, LEUKEMIA, CIRCULAR RNA, HeLa Cells
Male, Adenosine, BIOGENESIS, Nerve Tissue Proteins, Methyltransferases, RNA, Circular, M6A, Alternative Splicing, HEK293 Cells, Child, Preschool, Humans, Female, RNA Splicing Factors, back-splicing; cap-independent translation; circRNA; circRNA biogenesis; circRNA translation; epitrascriptome; m; 6; A modification; METTL3; YTHDC1, TRANSLATION, MESSENGER-RNA, LEUKEMIA, CIRCULAR RNA, HeLa Cells
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