MARTRE family proteins negatively regulate CCR4-NOT activity to protect poly(A) tail length and promote translation of maternal mRNA

Abstract The mammalian early embryo development requires translation of maternal mRNA inherited from the oocyte. While poly(A) tail length influences mRNA translation efficiency during the oocyte-to-embryo transition (OET), molecular mechanisms regulating maternal RNA poly(A) tail length are not ful...

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Main Authors: Jing Yang, Jiachen Bu, Bowen Liu, Yusheng Liu, Zhuqiang Zhang, Ziyi Li, Falong Lu, Bing Zhu, Yingfeng Li
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-55610-2
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author Jing Yang
Jiachen Bu
Bowen Liu
Yusheng Liu
Zhuqiang Zhang
Ziyi Li
Falong Lu
Bing Zhu
Yingfeng Li
author_facet Jing Yang
Jiachen Bu
Bowen Liu
Yusheng Liu
Zhuqiang Zhang
Ziyi Li
Falong Lu
Bing Zhu
Yingfeng Li
author_sort Jing Yang
collection DOAJ
description Abstract The mammalian early embryo development requires translation of maternal mRNA inherited from the oocyte. While poly(A) tail length influences mRNA translation efficiency during the oocyte-to-embryo transition (OET), molecular mechanisms regulating maternal RNA poly(A) tail length are not fully understood. In this study, we identified MARTRE, a previously uncharacterized protein family (MARTRE1-MARTRE6), as regulators expressed during mouse OET that modulate poly(A) tail length. MARTRE inhibits deadenylation through the direct interaction with the deadenylase CCR4-NOT, and ectopic expression of Martre stabilized mRNA by attenuating poly(A) tail shortening. Deletion of the Martre gene locus results in shortened poly(A) tails and decreased translation efficiency of actively translated mRNAs in mouse zygotes, but does not affect maternal mRNA decay. MARTRE proteins thus fine-tune maternal mRNA translation by negatively regulating the deadenylating activity of CCR4-NOT. Moreover, Martre knockout embryos show delayed 2-cell stage progression and compromised preimplantation development. Together, our findings highlight protection of long poly(A) tails from active deadenylation as an important mechanism to coordinate translation of maternal mRNA.
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spelling doaj-art-c73bda91b16b41c2b297e509254adc272025-08-20T01:47:59ZengNature PortfolioNature Communications2041-17232025-01-0116112310.1038/s41467-024-55610-2MARTRE family proteins negatively regulate CCR4-NOT activity to protect poly(A) tail length and promote translation of maternal mRNAJing Yang0Jiachen Bu1Bowen Liu2Yusheng Liu3Zhuqiang Zhang4Ziyi Li5Falong Lu6Bing Zhu7Yingfeng Li8Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of SciencesState Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of SciencesKey Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of SciencesCollege of Life Sciences, University of Chinese Academy of SciencesKey Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of SciencesAbstract The mammalian early embryo development requires translation of maternal mRNA inherited from the oocyte. While poly(A) tail length influences mRNA translation efficiency during the oocyte-to-embryo transition (OET), molecular mechanisms regulating maternal RNA poly(A) tail length are not fully understood. In this study, we identified MARTRE, a previously uncharacterized protein family (MARTRE1-MARTRE6), as regulators expressed during mouse OET that modulate poly(A) tail length. MARTRE inhibits deadenylation through the direct interaction with the deadenylase CCR4-NOT, and ectopic expression of Martre stabilized mRNA by attenuating poly(A) tail shortening. Deletion of the Martre gene locus results in shortened poly(A) tails and decreased translation efficiency of actively translated mRNAs in mouse zygotes, but does not affect maternal mRNA decay. MARTRE proteins thus fine-tune maternal mRNA translation by negatively regulating the deadenylating activity of CCR4-NOT. Moreover, Martre knockout embryos show delayed 2-cell stage progression and compromised preimplantation development. Together, our findings highlight protection of long poly(A) tails from active deadenylation as an important mechanism to coordinate translation of maternal mRNA.https://doi.org/10.1038/s41467-024-55610-2
spellingShingle Jing Yang
Jiachen Bu
Bowen Liu
Yusheng Liu
Zhuqiang Zhang
Ziyi Li
Falong Lu
Bing Zhu
Yingfeng Li
MARTRE family proteins negatively regulate CCR4-NOT activity to protect poly(A) tail length and promote translation of maternal mRNA
Nature Communications
title MARTRE family proteins negatively regulate CCR4-NOT activity to protect poly(A) tail length and promote translation of maternal mRNA
title_full MARTRE family proteins negatively regulate CCR4-NOT activity to protect poly(A) tail length and promote translation of maternal mRNA
title_fullStr MARTRE family proteins negatively regulate CCR4-NOT activity to protect poly(A) tail length and promote translation of maternal mRNA
title_full_unstemmed MARTRE family proteins negatively regulate CCR4-NOT activity to protect poly(A) tail length and promote translation of maternal mRNA
title_short MARTRE family proteins negatively regulate CCR4-NOT activity to protect poly(A) tail length and promote translation of maternal mRNA
title_sort martre family proteins negatively regulate ccr4 not activity to protect poly a tail length and promote translation of maternal mrna
url https://doi.org/10.1038/s41467-024-55610-2
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