Cargando…

Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Despic, Vladimir, Dejung, Mario, Gu, Mengting, Krishnan, Jayanth, Zhang, Jing, Herzel, Lydia, Straube, Korinna, Gerstein, Mark B., Butter, Falk, Neugebauer, Karla M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495070/
https://www.ncbi.nlm.nih.gov/pubmed/28381614
http://dx.doi.org/10.1101/gr.215954.116
_version_ 1783247757469810688
author Despic, Vladimir
Dejung, Mario
Gu, Mengting
Krishnan, Jayanth
Zhang, Jing
Herzel, Lydia
Straube, Korinna
Gerstein, Mark B.
Butter, Falk
Neugebauer, Karla M.
author_facet Despic, Vladimir
Dejung, Mario
Gu, Mengting
Krishnan, Jayanth
Zhang, Jing
Herzel, Lydia
Straube, Korinna
Gerstein, Mark B.
Butter, Falk
Neugebauer, Karla M.
author_sort Despic, Vladimir
collection PubMed
description 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 of pri-mir-430 transcripts, 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.
format Online
Article
Text
id pubmed-5495070
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-54950702018-01-01 Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition Despic, Vladimir Dejung, Mario Gu, Mengting Krishnan, Jayanth Zhang, Jing Herzel, Lydia Straube, Korinna Gerstein, Mark B. Butter, Falk Neugebauer, Karla M. Genome Res Research 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 of pri-mir-430 transcripts, 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. Cold Spring Harbor Laboratory Press 2017-07 /pmc/articles/PMC5495070/ /pubmed/28381614 http://dx.doi.org/10.1101/gr.215954.116 Text en © 2017 Despic et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Despic, Vladimir
Dejung, Mario
Gu, Mengting
Krishnan, Jayanth
Zhang, Jing
Herzel, Lydia
Straube, Korinna
Gerstein, Mark B.
Butter, Falk
Neugebauer, Karla M.
Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition
title Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition
title_full Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition
title_fullStr Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition
title_full_unstemmed Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition
title_short Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition
title_sort dynamic rna–protein interactions underlie the zebrafish maternal-to-zygotic transition
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495070/
https://www.ncbi.nlm.nih.gov/pubmed/28381614
http://dx.doi.org/10.1101/gr.215954.116
work_keys_str_mv AT despicvladimir dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition
AT dejungmario dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition
AT gumengting dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition
AT krishnanjayanth dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition
AT zhangjing dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition
AT herzellydia dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition
AT straubekorinna dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition
AT gersteinmarkb dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition
AT butterfalk dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition
AT neugebauerkarlam dynamicrnaproteininteractionsunderliethezebrafishmaternaltozygotictransition