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Updated: May 5, 2026

A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation
Jianzhao Liu1, Yanan Yue1, Dali Han2
11] Department of Chemistry, University of Chicago, Chicago, Illinois, USA. [2] Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois, USA. [3].
Abstract:
N(6)-methyladenosine (m(6)A) is the most prevalent and reversible internal modification in mammalian messenger and noncoding RNAs. We report here that human methyltransferase-like 14 (METTL14) catalyzes m(6)A RNA methylation. Together with METTL3, the only previously known m(6)A methyltransferase, these two proteins form a stable heterodimer core complex of METTL3-METTL14 that functions in cellular m(6)A deposition on mammalian nuclear RNAs. WTAP, a mammalian splicing factor, can interact with this complex and affect this methylation.
Insights
Methyltransferase-like 14 (METTL14) is identified as a key enzyme in catalyzing N(6)-methyladenosine (m(6)A) RNA methylation. This protein forms a complex with METTL3, crucial for m(6)A deposition in mammalian cells.
Area of Science:
- Biochemistry
- Molecular Biology
- Epigenetics
Background:
- N(6)-methyladenosine (m(6)A) is the most abundant internal RNA modification in eukaryotes.
- m(6)A is dynamically regulated and plays critical roles in various cellular processes.
- The enzymes responsible for m(6)A deposition were not fully characterized.
Purpose of the Study:
- To identify and characterize novel components of the m(6)A methyltransferase complex.
- To elucidate the function of METTL14 in m(6)A RNA methylation.
Main Methods:
- Protein complex purification and characterization.
- In vitro RNA methylation assays.
- Analysis of protein-protein interactions.
Main Results:
- Human methyltransferase-like 14 (METTL14) was found to catalyze m(6)A RNA methylation.
- METTL14 forms a stable heterodimer with METTL3, the previously known m(6)A methyltransferase.
- The METTL3-METTL14 complex is responsible for cellular m(6)A deposition on mammalian nuclear RNAs.
- WTAP, a splicing factor, interacts with the METTL3-METTL14 complex and influences m(6)A methylation.
Conclusions:
- METTL14 is a crucial component of the m(6)A methyltransferase complex.
- The METTL3-METTL14 heterodimer is the core catalytic unit for m(6)A methylation in mammalian cells.
- WTAP modulates the activity of the m(6)A methyltransferase complex.
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