CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts

The maternal-to-zygotic transition (MZT) is a reprograming process encompassing zygotic genome activation (ZGA) and the clearance of maternally-provided mRNAs. While some factors regulating MZT have been identified, there are thousands of maternal RNAs whose function has not been ascribed yet. Here,...

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Detalles Bibliográficos
Autores: Hernández Huertas, Luis, Moreno Sánchez, Ismael, Crespo-Cuadrado, Jesús, Vargas-Barco, Ana, da Silva Pescador, Gabriel, Zhang, Ying, Wen, Zhihui, Florens, Laurence, Santos Pereira, José María, Bazzini, Ariel A., Moreno Mateos, Miguel Ángel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/180448
Acceso en línea:https://hdl.handle.net/11441/180448
https://doi.org/10.1038/s44318-025-00617-8
Access Level:acceso abierto
Palabra clave:CRISPR-RfxCas13d
MZT
Kinases
Bckdk
Zebrafish
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spelling CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleostsHernández Huertas, LuisMoreno Sánchez, IsmaelCrespo-Cuadrado, JesúsVargas-Barco, Anada Silva Pescador, GabrielZhang, YingWen, ZhihuiFlorens, LaurenceSantos Pereira, José MaríaBazzini, Ariel A.Moreno Mateos, Miguel ÁngelCRISPR-RfxCas13dMZTKinasesBckdkZebrafishThe maternal-to-zygotic transition (MZT) is a reprograming process encompassing zygotic genome activation (ZGA) and the clearance of maternally-provided mRNAs. While some factors regulating MZT have been identified, there are thousands of maternal RNAs whose function has not been ascribed yet. Here, we have performed a proof-of-principle CRISPR-RfxCas13d maternal screen, in which we targeted mRNAs encoding kinases and phosphatases or proteins regulating them in zebrafish. This screen identified branched-chain ketoacid dehydrogenase kinase, Bckdk, as a novel post-translational regulator of MZT. Bckdk mRNA knockdown caused epiboly defects, ZGA deregulation, H3K27ac reduction and a partial impairment of miR-430 processing. Phospho-proteomic analysis revealed that Phf10/Baf45a, a chromatin remodeling factor, is less phosphorylated upon Bckdk depletion. Further, phf10 mRNA knockdown also altered ZGA, and expression of a phospho-mimetic mutant of Phf10 rescued the developmental defects observed after bckdk mRNA depletion, as well as restored H3K27ac levels. Altogether, our results demonstrate the competence of CRISPR-RfxCas13d screenings to uncover new regulators of early vertebrate development and shed light on the post-translational control of MZT mediated by protein phosphorylation.Springer NatureBiología CelularEC | NextGenerationEU (NGEU)2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/180448https://doi.org/10.1038/s44318-025-00617-8reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésEmbo Journal, 44 (23), 7021-7059.PRTR-C17.I1https://link.springer.com/article/10.1038/s44318-025-00617-8info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1804482026-06-17T12:51:07Z
dc.title.none.fl_str_mv CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts
title CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts
spellingShingle CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts
Hernández Huertas, Luis
CRISPR-RfxCas13d
MZT
Kinases
Bckdk
Zebrafish
title_short CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts
title_full CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts
title_fullStr CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts
title_full_unstemmed CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts
title_sort CRISPR-RfxCas13d screening uncovers Bckdk as a post-translational regulator of maternal-to-zygotic transition in teleosts
dc.creator.none.fl_str_mv Hernández Huertas, Luis
Moreno Sánchez, Ismael
Crespo-Cuadrado, Jesús
Vargas-Barco, Ana
da Silva Pescador, Gabriel
Zhang, Ying
Wen, Zhihui
Florens, Laurence
Santos Pereira, José María
Bazzini, Ariel A.
Moreno Mateos, Miguel Ángel
author Hernández Huertas, Luis
author_facet Hernández Huertas, Luis
Moreno Sánchez, Ismael
Crespo-Cuadrado, Jesús
Vargas-Barco, Ana
da Silva Pescador, Gabriel
Zhang, Ying
Wen, Zhihui
Florens, Laurence
Santos Pereira, José María
Bazzini, Ariel A.
Moreno Mateos, Miguel Ángel
author_role author
author2 Moreno Sánchez, Ismael
Crespo-Cuadrado, Jesús
Vargas-Barco, Ana
da Silva Pescador, Gabriel
Zhang, Ying
Wen, Zhihui
Florens, Laurence
Santos Pereira, José María
Bazzini, Ariel A.
Moreno Mateos, Miguel Ángel
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Biología Celular
EC | NextGenerationEU (NGEU)
dc.subject.none.fl_str_mv CRISPR-RfxCas13d
MZT
Kinases
Bckdk
Zebrafish
topic CRISPR-RfxCas13d
MZT
Kinases
Bckdk
Zebrafish
description The maternal-to-zygotic transition (MZT) is a reprograming process encompassing zygotic genome activation (ZGA) and the clearance of maternally-provided mRNAs. While some factors regulating MZT have been identified, there are thousands of maternal RNAs whose function has not been ascribed yet. Here, we have performed a proof-of-principle CRISPR-RfxCas13d maternal screen, in which we targeted mRNAs encoding kinases and phosphatases or proteins regulating them in zebrafish. This screen identified branched-chain ketoacid dehydrogenase kinase, Bckdk, as a novel post-translational regulator of MZT. Bckdk mRNA knockdown caused epiboly defects, ZGA deregulation, H3K27ac reduction and a partial impairment of miR-430 processing. Phospho-proteomic analysis revealed that Phf10/Baf45a, a chromatin remodeling factor, is less phosphorylated upon Bckdk depletion. Further, phf10 mRNA knockdown also altered ZGA, and expression of a phospho-mimetic mutant of Phf10 rescued the developmental defects observed after bckdk mRNA depletion, as well as restored H3K27ac levels. Altogether, our results demonstrate the competence of CRISPR-RfxCas13d screenings to uncover new regulators of early vertebrate development and shed light on the post-translational control of MZT mediated by protein phosphorylation.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/180448
https://doi.org/10.1038/s44318-025-00617-8
url https://hdl.handle.net/11441/180448
https://doi.org/10.1038/s44318-025-00617-8
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Embo Journal, 44 (23), 7021-7059.
PRTR-C17.I1
https://link.springer.com/article/10.1038/s44318-025-00617-8
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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