mA-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition.

Nature 2017 02 13;542(7642):475-478. Epub 2017 Feb 13.

Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.

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 N-methyladenosine (mA) modified, and the clearance of these maternal mRNAs is facilitated by an mA-binding protein, Ythdf2. Removal of Ythdf2 in zebrafish embryos decelerates the decay of mA-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 mA-dependent RNA decay as a previously unidentified maternally driven mechanism that regulates maternal mRNA clearance during zebrafish MZT, highlighting the critical role of mA mRNA methylation in transcriptome switching and animal development.

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http://dx.doi.org/10.1038/nature21355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323276PMC
February 2017
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