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A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
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Modulation of circRNA Metabolism by m6A Modification
Gaia Di Timoteo1, Dario Dattilo1, Alvaro Centrón-Broco1
1Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, Rome, Italy.
Cell Reports
|May 14, 2020
Summary
N6-methyladenosine (m6A) RNA modifications regulate circular RNA (circRNA) biogenesis and translation. METTL3 and YTHDC1 are crucial for circRNA formation, while m6A influences circRNA translation via YTHDF3 and eIF4G2.
Area of Science:
- Molecular Biology
- RNA Biology
- Epigenetics
Background:
- N6-methyladenosine (m6A) is a prevalent RNA modification impacting mRNA metabolism.
- The role of m6A in circular RNA (circRNA) biogenesis and function remains largely unexplored.
- circRNAs are formed through back-splicing, a process distinct from linear mRNA splicing.
Purpose of the Study:
- To investigate the role of m6A in the biogenesis and function of circRNAs.
- To identify specific m6A sites and associated proteins regulating circRNA formation and translation.
- To elucidate the mechanisms by which m6A controls circRNA accumulation and translation.
Main Methods:
- Case study using circ-ZNF609.
- Investigated the requirement of METTL3 and YTHDC1 in back-splicing.
- Analyzed the correlation between METTL3, YTHDC1 binding, and m6A exon back-splicing.
- Studied the impact of m6A on circRNA translation using YTHDF3 and eIF4G2.
Main Results:
- Specific m6A sites were found to control circ-ZNF609 accumulation.
- METTL3 and YTHDC1 are essential for directing the back-splicing reaction in circRNA biogenesis.
- A direct correlation exists between METTL3 requirement, YTHDC1 binding, and m6A exon back-splicing efficiency.
- m6A modifications modulate the translation of circ-ZNF609 through YTHDF3 and eIF4G2 recognition.
Conclusions:
- m6A modification plays a critical role in both the biogenesis and translation of circRNAs.
- METTL3 and YTHDC1 are key regulators of m6A-dependent circRNA formation.
- m6A acts as a regulatory switch for circRNA translation, impacting downstream cellular functions.
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