m 6 A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition

Nature. 2017 Feb 23;542(7642):475-478. doi: 10.1038/nature21355. Epub 2017 Feb 13.


The maternal-to-zygotic transition (MZT) is one of the most profound and tightly orchestrated processes during the early life of embryos, yet factors that shape the temporal pattern of vertebrate MZT are largely unknown. Here we show that over one-third of zebrafish maternal messenger RNAs (mRNAs) can be N6-methyladenosine (m6A) modified, and the clearance of these maternal mRNAs is facilitated by an m6A-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of m6A-modified maternal mRNAs and impedes zygotic genome activation. These embryos fail to initiate timely MZT, undergo cell-cycle pause, and remain developmentally delayed throughout larval life. Our study reveals m6A-dependent RNA decay as a previously unidentified maternally driven mechanism that regulates maternal mRNA clearance during zebrafish MZT, highlighting the critical role of m6A mRNA methylation in transcriptome switching and animal development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / metabolism
  • Animals
  • Embryonic Development / genetics*
  • Female
  • Male
  • RNA Stability*
  • RNA, Messenger, Stored / chemistry
  • RNA, Messenger, Stored / genetics
  • RNA, Messenger, Stored / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Time Factors
  • Zebrafish / embryology*
  • Zebrafish / genetics*
  • Zebrafish Proteins / deficiency
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zygote / metabolism*


  • RNA, Messenger, Stored
  • RNA-Binding Proteins
  • Ythdf2 protein, zebrafish
  • Zebrafish Proteins
  • N6-methyladenosine (m6A)
  • Adenosine