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Updated: Jun 22, 2025

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
RNA Binding by the m6A Methyltransferases METTL16 and METTL3
1Biochemistry and Molecular Biology Department, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Abstract:
Methyltransferases are a wide-ranging, yet well-conserved, class of molecules that have been found to modify a wide variety of substrates. Interest in RNA methylation has surged in recent years with the identification of the major eukaryotic mRNA m6A methyltransferase METTL3. METTL16 has also been identified as an RNA m6A methyltransferase; however, much less is known about its targets and actions. Interestingly, in addition to their catalytic activities, both METTL3 and METTL16 also have "methylation-independent" functions, including translational regulation, which have been discovered. However, evidence suggests that METTL16's role as an RNA-binding protein may be more significant than is currently recognized. In this review, we will introduce RNA methylation, specifically m6A, and the enzymes responsible for its deposition. We will discuss the varying roles that these enzymes perform and delve deeper into their RNA targets and possible roles as methylation-independent RNA binding proteins. Finally, we will touch upon the many open questions still remaining.
Insights
Methyltransferases like METTL3 and METTL16 modify RNA, with METTL16
Area of Science:
- Biochemistry
- Molecular Biology
- Epigenetics
Background:
- Methyltransferases are conserved enzymes modifying diverse substrates.
- RNA methylation, particularly N6-methyladenosine (m6A), is crucial in eukaryotes.
- METTL3 is the primary eukaryotic mRNA m6A methyltransferase; METTL16 also methylates RNA but is less understood.
Purpose of the Study:
- To review RNA methylation, focusing on m6A.
- To discuss the roles and targets of RNA methyltransferases, specifically METTL3 and METTL16.
- To explore the methylation-independent functions of these enzymes, particularly METTL16's RNA-binding capabilities.
Main Methods:
- Literature review of methyltransferase functions and RNA targets.
- Analysis of existing research on METTL3 and METTL16.
- Discussion of experimental evidence for methylation-dependent and -independent roles.
Main Results:
- METTL3 and METTL16 are key RNA m6A methyltransferases.
- Both enzymes exhibit methylation-independent functions, including translational regulation.
- METTL16's role as an RNA-binding protein may be more significant than previously recognized.
Conclusions:
- RNA methylation is a vital regulatory mechanism.
- METTL3 and METTL16 possess diverse functions beyond catalysis.
- Further research is needed to fully elucidate METTL16's targets and RNA-binding roles.
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