Zc3h13/Flacc is required for adenosine methylation by bridging the mRNA-binding factor Rbm15/Spenito to the m6A machinery component Wtap/Fl(2)d

Genes Dev. 2018 Mar 1;32(5-6):415-429. doi: 10.1101/gad.309146.117. Epub 2018 Mar 13.


N6-methyladenosine (m6A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m6A is catalyzed by the activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor of m6A methyltransferase complex components in Drosophila and mice. Like other components of this complex, Flacc controls m6A levels and is involved in sex determination in Drosophila We demonstrate that Flacc promotes m6A deposition by bridging Fl(2)d to the mRNA-binding factor Nito. Altogether, our work advances the molecular understanding of conservation and regulation of the m6A machinery.

Keywords: Flacc; RNA modifications; Zc3h13; m6A; methyltransferase complex; sex determination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / physiology*
  • Gene Expression Regulation, Developmental
  • Methylation
  • Methyltransferases / metabolism*
  • Mice
  • Mouse Embryonic Stem Cells
  • Nuclear Proteins / metabolism*
  • Protein Transport
  • RNA Precursors / genetics
  • RNA Splicing
  • RNA Splicing Factors
  • RNA-Binding Proteins / metabolism*
  • Sex Determination Processes / genetics


  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • NITO protein, Drosophila
  • Nuclear Proteins
  • RNA Precursors
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • Rbm15 protein, mouse
  • Wtap protein, mouse
  • Zc3h13 protein, mouse
  • Methyltransferases
  • Mettl3 protein, mouse
  • Adenosine