ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development

Abstract Background During meiosis, the oocyte genome keeps dormant for a long time until zygotic genome activation. The dynamics and homeostasis of the maternal transcriptome are essential for maternal-to-zygotic transition. Zygotic arrest 1 (ZAR1) and its homolog, ZAR2, are RNA-binding proteins th...

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Main Authors: Yu-Ke Wu, Ruibao Su, Zhi-Yan Jiang, Yun-Wen Wu, Yan Rong, Shu-Yan Ji, Jingwen Liu, Zhuoyue Niu, Zhiyi Li, Yuanchao Xue, Falong Lu, Heng-Yu Fan
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Genome Biology
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Online Access:https://doi.org/10.1186/s13059-025-03593-8
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author Yu-Ke Wu
Ruibao Su
Zhi-Yan Jiang
Yun-Wen Wu
Yan Rong
Shu-Yan Ji
Jingwen Liu
Zhuoyue Niu
Zhiyi Li
Yuanchao Xue
Falong Lu
Heng-Yu Fan
author_facet Yu-Ke Wu
Ruibao Su
Zhi-Yan Jiang
Yun-Wen Wu
Yan Rong
Shu-Yan Ji
Jingwen Liu
Zhuoyue Niu
Zhiyi Li
Yuanchao Xue
Falong Lu
Heng-Yu Fan
author_sort Yu-Ke Wu
collection DOAJ
description Abstract Background During meiosis, the oocyte genome keeps dormant for a long time until zygotic genome activation. The dynamics and homeostasis of the maternal transcriptome are essential for maternal-to-zygotic transition. Zygotic arrest 1 (ZAR1) and its homolog, ZAR2, are RNA-binding proteins that are important for the regulation of maternal mRNA stability. Results Smart-seq2 analysis reveals drastically downregulated maternal transcripts. However, the detection of transcript levels by Smart-seq2 may be biased by the polyadenylated tail length of the mRNAs. Similarly, differential expression of maternal transcripts in oocytes with or without Zar1/2 differs when analyzed using total RNA-seq and Smart-seq2, suggesting an influence of polyadenylation. Combined analyses using total RNA-seq, LACE-seq, PAIso-seq2, and immunoprecipitation-mass spectrometry reveals that ZAR1 may target the 3’-untranslated regions of maternal transcripts, regulates their stability in germinal vesicle stage oocytes, and interacts with other proteins to control the polyadenylation of mRNAs. Conclusions The jointly analyzed multi-omics data highlight the limitations of Smart-seq2 in oocytes, clarify the dynamics of the maternal transcriptome, and uncover new roles of ZAR1 in regulating the maternal transcriptome.
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spelling doaj-art-a9c19585692d44b59d678046e1b6b55f2025-08-20T02:15:11ZengBMCGenome Biology1474-760X2025-05-0126112810.1186/s13059-025-03593-8ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte developmentYu-Ke Wu0Ruibao Su1Zhi-Yan Jiang2Yun-Wen Wu3Yan Rong4Shu-Yan Ji5Jingwen Liu6Zhuoyue Niu7Zhiyi Li8Yuanchao Xue9Falong Lu10Heng-Yu Fan11MOE Key Laboratory for Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang UniversityKey Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of SciencesMOE Key Laboratory for Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang UniversityMOE Key Laboratory for Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang UniversityMOE Key Laboratory for Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang UniversityInstitute of Medical Genetics and Development, Key Laboratory of Reproductive Genetics (Ministry of Education) and Women’s Hospital, Zhejiang University School of MedicineState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental BiologyState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental BiologyDepartment of Computer Science and Engineering, College of Engineering, The Ohio State University-ColumbusKey Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of SciencesState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental BiologyMOE Key Laboratory for Biosystems Homeostasis and Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang UniversityAbstract Background During meiosis, the oocyte genome keeps dormant for a long time until zygotic genome activation. The dynamics and homeostasis of the maternal transcriptome are essential for maternal-to-zygotic transition. Zygotic arrest 1 (ZAR1) and its homolog, ZAR2, are RNA-binding proteins that are important for the regulation of maternal mRNA stability. Results Smart-seq2 analysis reveals drastically downregulated maternal transcripts. However, the detection of transcript levels by Smart-seq2 may be biased by the polyadenylated tail length of the mRNAs. Similarly, differential expression of maternal transcripts in oocytes with or without Zar1/2 differs when analyzed using total RNA-seq and Smart-seq2, suggesting an influence of polyadenylation. Combined analyses using total RNA-seq, LACE-seq, PAIso-seq2, and immunoprecipitation-mass spectrometry reveals that ZAR1 may target the 3’-untranslated regions of maternal transcripts, regulates their stability in germinal vesicle stage oocytes, and interacts with other proteins to control the polyadenylation of mRNAs. Conclusions The jointly analyzed multi-omics data highlight the limitations of Smart-seq2 in oocytes, clarify the dynamics of the maternal transcriptome, and uncover new roles of ZAR1 in regulating the maternal transcriptome.https://doi.org/10.1186/s13059-025-03593-8Maternal-to-zygotic transitionMeiosisRNA-binding proteinsRNA polyadenylationOocyte transcriptome
spellingShingle Yu-Ke Wu
Ruibao Su
Zhi-Yan Jiang
Yun-Wen Wu
Yan Rong
Shu-Yan Ji
Jingwen Liu
Zhuoyue Niu
Zhiyi Li
Yuanchao Xue
Falong Lu
Heng-Yu Fan
ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development
Genome Biology
Maternal-to-zygotic transition
Meiosis
RNA-binding proteins
RNA polyadenylation
Oocyte transcriptome
title ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development
title_full ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development
title_fullStr ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development
title_full_unstemmed ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development
title_short ZAR1 and ZAR2 orchestrate the dynamics of maternal mRNA polyadenylation during mouse oocyte development
title_sort zar1 and zar2 orchestrate the dynamics of maternal mrna polyadenylation during mouse oocyte development
topic Maternal-to-zygotic transition
Meiosis
RNA-binding proteins
RNA polyadenylation
Oocyte transcriptome
url https://doi.org/10.1186/s13059-025-03593-8
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