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

Autor:	Hernandez-Huertas L; Andalusian Center for Developmental Biology (CABD), Pablo de Olavide University/CSIC/Junta de Andalucía, Ctra. Utrera Km.1, 41013, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Pablo de Olavide University, Ctra. Utrera Km.1, 41013, Seville, Spain., Moreno-Sanchez I; Andalusian Center for Developmental Biology (CABD), Pablo de Olavide University/CSIC/Junta de Andalucía, Ctra. Utrera Km.1, 41013, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Pablo de Olavide University, Ctra. Utrera Km.1, 41013, Seville, Spain., Crespo-Cuadrado J; Andalusian Center for Developmental Biology (CABD), Pablo de Olavide University/CSIC/Junta de Andalucía, Ctra. Utrera Km.1, 41013, Seville, Spain., Vargas-Baco A; Andalusian Center for Developmental Biology (CABD), Pablo de Olavide University/CSIC/Junta de Andalucía, Ctra. Utrera Km.1, 41013, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Pablo de Olavide University, Ctra. Utrera Km.1, 41013, Seville, Spain., da Silva Pescador G; Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO 64110, USA., Santos-Pereira JM; Andalusian Center for Developmental Biology (CABD), Pablo de Olavide University/CSIC/Junta de Andalucía, Ctra. Utrera Km.1, 41013, Seville, Spain., Bazzini AA; Stowers Institute for Medical Research, 1000 E 50th St, Kansas City, MO 64110, USA.; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA., Moreno-Mateos MA; Andalusian Center for Developmental Biology (CABD), Pablo de Olavide University/CSIC/Junta de Andalucía, Ctra. Utrera Km.1, 41013, Seville, Spain.; Department of Molecular Biology and Biochemical Engineering, Pablo de Olavide University, Ctra. Utrera Km.1, 41013, Seville, Spain.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 May 23. Date of Electronic Publication: 2024 May 23.
DOI:	10.1101/2024.05.22.595167
Abstrakt:	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 screening targeting mRNAs encoding protein kinases and phosphatases in zebrafish and identified 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 Phf10 constitutively phosphorylated rescued the developmental defects observed after bckdk mRNA depletion. 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. Competing Interests: Declaration of interests The authors declare no competing interests.
Databáze:	MEDLINE
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