title: Dynamic RNA-protein interactions underlie the zebrafish maternal-to-zygotic transition.
abstract: During the maternal-to-zygotic transition (MZT), transcriptionally silent embryos rely on post-transcriptional regulation of maternal mRNAs until zygotic genome activation (ZGA). RNA-binding proteins (RBPs) are important regulators of post-transcriptional RNA processing events, yet their identities and functions during developmental transitions in vertebrates remain largely unexplored. Using mRNA interactome capture, we identified 227 RBPs in zebrafish embryos before and during ZGA, hereby named the zebrafish MZT mRNA-bound proteome. This protein constellation consists of many conserved RBPs, some of which are potential stage-specific mRNA interactors that likely reflect the dynamics of RNA-protein interactions during MZT. The enrichment of numerous splicing factors like hnRNP proteins before ZGA was surprising, because maternal mRNAs were found to be fully spliced. To address potentially unique roles of these RBPs in embryogenesis, we focused on Hnrnpa1. iCLIP and subsequent mRNA reporter assays revealed a function for Hnrnpa1 in the regulation of poly(A) tail length and translation of maternal mRNAs through sequence-specific association with 3' UTRs before ZGA. Comparison of iCLIP data from two developmental stages revealed that Hnrnpa1 dissociates from maternal mRNAs at ZGA and instead regulates the nuclear processing ofpri-mir-430transcripts, which we validated experimentally. The shift from cytoplasmic to nuclear RNA targets was accompanied by a dramatic translocation of Hnrnpa1 and other pre-mRNA splicing factors to the nucleus in a transcription-dependent manner. Thus, our study identifies global changes in RNA-protein interactions during vertebrate MZT and shows that Hnrnpa1 RNA-binding activities are spatially and temporally coordinated to regulate RNA metabolism during early development.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Despic
authors.affiliation: Institute of Molecular Biology, 55128 Mainz, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Dejung
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.|Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Mengting
authors.initials: M
authors.lastname: Gu
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.|Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Jayanth
authors.initials: J
authors.lastname: Krishnan
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.|Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Lydia
authors.initials: L
authors.lastname: Herzel
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Korinna
authors.initials: K
authors.lastname: Straube
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.|Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
authors.affiliation: Institute of Molecular Biology, 55128 Mainz, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Butter
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Karla M
authors.initials: KM
authors.lastname: Neugebauer
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D015053:Zygote / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D035683:MicroRNAs; C557527:Mirn430 microRNA, zebrafish; D029961:Zebrafish Proteins