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].

Nature Chemical Biology
|December 10, 2013
PubMed

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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