title: m6A-dependent maternal mRNA clearance facilitates zebrafish maternal-to-zygotic transition.
abstract: 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.
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Boxuan Simen
authors.initials: BS
authors.lastname: Zhao
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Organismal Biology and Anatomy, The University of Chicago, 1027 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Alana V
authors.initials: AV
authors.lastname: Beadell
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Zhike
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Hailing
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Organismal Biology and Anatomy, The University of Chicago, 1027 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Kuuspalu
authors.affiliation: Department of Organismal Biology and Anatomy, The University of Chicago, 1027 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ho
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.|Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.
authors.forename: Chuan
authors.initials: C
authors.lastname: He
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D008297:Male; D020871:RNA Stability; D023121:RNA, Messenger, Stored / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015053:Zygote / Q000378:metabolism*
chemical_list: D023121:RNA, Messenger, Stored; D016601:RNA-Binding Proteins; C000621269:Ythdf2 protein, zebrafish; D029961:Zebrafish Proteins; C010223:N-methyladenosine; D000241:Adenosine