scholarly journals Abundant non-A residues in the poly(A) tail orchestrate the mouse oocyte-to-embryo transition

2021 ◽  
Author(s):  
Yusheng Liu ◽  
Hu Nie ◽  
Le-Yun Wang ◽  
Shuang Wu ◽  
Wei Li ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
General Pattern ◽  
Mrna Translation ◽  
Tail Length ◽  
Maternal Rna ◽  
Rna Transcripts ◽  
Maternal Mrna ◽  
Genome Wide ◽  
Post Transcriptional Regulation ◽  
Genome Activation

Non-A (U, G, and C) residues can be added to the 5-end, internal, and 3-end positions of poly(A) tails of RNA transcripts, and some of these have been shown to regulate mRNA stability. The mammalian oocyte-to-embryo transition (OET) relies on post-transcriptional regulation of maternal RNA, because transcription is silent during this process until the point of zygotic genome activation (ZGA). Although the regulation of mRNA translation by poly(A) tail length plays an important role in the mammalian OET, the dynamics and functions of non-A residues in poly(A) tails are completely unknown. In this study, we profiled the genome-wide presence, abundance, and roles of non-A residues during the OET in mice using PAIso-seq1 and PAIso-seq, two complementary methods of poly(A) tail analysis. We found that non-A residues are highly dynamic in maternal mRNA, following a general pattern of beginning to increase at the MII stage, becoming highly abundant after fertilization with U residues in about half of poly(A) tails in 1-cell embryos, and declining in 2-cell embryos. We revealed that Btg4-mediated global maternal mRNA deadenylation created the substrates for U residue addition by Tut4/7 at their 3-ends and further re-polyadenylation. In addition, G residues can be added by Tent4a/b. Finally, we demonstrate that G residues stabilize the modified mRNA, while the U residues mark maternal RNA for faster degradation in 2-cell mouse embryos. Taken together, these findings demonstrate that non-A residues are abundant and re-sculpt the maternal transcriptome to initiate zygotic development, which reveals the functional importance of the post-transcriptional regulation mediated by non-A residues in mRNA poly(A) tails.

scholarly journals Poly(A) tail length is a major regulator of maternal gene expression during the mammalian oocyte-to-embryo transition

2021 ◽  
Author(s):  
Yusheng Liu ◽  
Hu Nie ◽  
Chuanxin Zhang ◽  
Zhenzhen Hou ◽  
Jiaqiang Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Tail Length ◽  
Human Embryos ◽  
Molecular Evidence ◽  
Translational Efficiency ◽  
Mammalian Oocyte ◽  
Maternal Mrna ◽  
Polyadenylation Sites ◽  
Post Transcriptional Regulation

AbstractTranscription is silent during the mammalian oocyte-to-embryo transition (OET) until zygotic genome activation (ZGA). Therefore, the OET relies on post-transcriptional regulation of maternal mRNA, among which poly(A) tail lengths have been found to regulate translation for a small number of genes1–3. However, transcriptome-wide poly(A) tail length dynamics and their role in gene expression during the mammalian OET remain unknown. Here, we quantified transcriptome-wide mRNA poly(A) tail length dynamics during the mammalian OET using PAIso-seq1 and PAIso-seq24,5, two methods with different underlying principles that preserve the poly(A) tail information. We revealed that poly(A) tail length was highly dynamic during the mouse OET, and Btg4 is responsible for global maternal mRNA deadenylation. We found that the poly(A) tail length positively associated with translational efficiency transcriptome-wide in mouse oocytes. In addition, genes with different alternative polyadenylation isoforms show longer poly(A) tails for isoforms with distal polyadenylation sites compared to those with proximal polyadenylation sites in mouse, rat, pig and human oocytes after meiotic resumption, which is not seen in cultured cell lines. Surprisingly, mammalian embryos, namely mouse, rat, pig, and human embryos, all experience highly conserved global mRNA re-polyadenylation after fertilization, providing molecular evidence that the early embryo development before ZGA is driven by re-polyadenylated maternal mRNAs rather than newly transcribed mRNAs. Together, our study reveals the conserved mRNA poly(A) tail length landscape. This resource can be used for exploring spatiotemporal post-transcriptional regulation throughout the mammalian OET.

scholarly journals Conservation and divergence of poly(A) tail regulation during the mammalian oocyte-to-embryo transition

2021 ◽  
Author(s):  
Yusheng Liu ◽  
Junxue Jin ◽  
Yiwei Zhang ◽  
Le-Yun Wang ◽  
Chuanxin Zhang ◽  
...  
Keyword(s):  
Length Distribution ◽  
Tail Length ◽  
Mammal Species ◽  
Mammalian Oocyte ◽  
Maternal Mrna ◽  
Post Transcriptional Regulation ◽  
Genome Activation ◽  
Parthenogenetic Embryos ◽  
Zygotic Genome

SUMMARYPoly(A) tail length and non-A residues are vital for oocyte-to-embryo transition (OET) in mice and humans1–5. However, the role of poly(A) tail length and non-A residues during OET in other commonly used mammalian animal models for human diseases remains unexplored. In addition, the degree of conservation in maternal mRNA poly(A) tail dynamics during OET across different mammal species is unknown. Here, we conduct a comparative analysis of the poly(A) tails during OET across four species: mice, rats, pigs, and humans. Dynamics during OET found to be conserved across all four species include: maternal mRNA deadenylation during oocyte maturation and re-polyadenylation after fertilization; a fall-rise trend in poly(A) tail length distribution; a rise-fall trend in the ratio of poly(A) tails with non-A residues; higher abundance of non-A residues in poly(A) tails of maternal mRNA than in zygotic genome activation (ZGA) mRNA; maternal mRNA with U residues degrades faster than those without U residues at the stage when ZGA takes place. While in mice and rats maternal mRNA deadenylation is impaired in parthenogenetic embryos and ZGA inhibition leads to blocked maternal mRNA deadenylation in mice and humans. In contrast, the length of consecutive U residues and the duration time of U residues in poly(A) tail diverges across the four species. Together, these findings reveal that the poly(A) tail mediated maternal mRNA post-transcriptional regulation is highly conserved in mammals with unique divergences in the length and life-span of U residues, providing new insights for the further understanding of OET across different mammals.

scholarly journals Genome-wide analysis reveals a switch in the translational program upon oocyte meiotic resumption

2019 ◽  
Author(s):  
Xuan G. Luong ◽  
Enrico Maria Daldello ◽  
Gabriel Rajkovic ◽  
Cai-Rong Yang ◽  
Marco Conti
Keyword(s):  
Mrna Translation ◽  
Messenger Rnas ◽  
Rna Seq ◽  
Genome Wide Analysis ◽  
Meiotic Progression ◽  
Maternal Mrna ◽  
Highly Active ◽  
Genome Wide ◽  
Molecular Machinery ◽  
Maternal Mrnas

SummaryDuring oocyte maturation, changes in gene expression depend exclusively on translation and degradation of maternal mRNAs rather than transcription. Execution of this translation program is essential for assembling the molecular machinery required for meiotic progression, fertilization, and embryo development. With the present study, we used a RiboTag/RNA-Seq approach to explore the timing of maternal mRNA translation in quiescent oocytes as well as in oocytes progressing through the first meiotic division. This genome-wide analysis reveals a global switch in maternal mRNA translation coinciding with oocyte re-entry into the meiotic cell cycle. Messenger RNAs whose translation is highly active in quiescent oocytes invariably become repressed during meiotic re-entry, whereas transcripts repressed in quiescent oocytes become activated. Experimentally, we have defined the exact timing of the switch, the repressive function of CPE elements, and identified a novel role for CPEB1 in maintaining constitutive translation of a large group of maternal mRNAs during maturation.

scholarly journals Dynamics of mitochondrial mRNA abundance and poly(A) tail during the mammalian oocyte-to-embryo transition

2021 ◽  
Author(s):  
Yusheng Liu ◽  
Yiwei Zhang ◽  
Zhonghua Liu ◽  
Falong Lu ◽  
Jiaqiang Wang
Keyword(s):  
Cell Lines ◽  
Posttranscriptional Regulation ◽  
Tricarboxylic Acid Cycle ◽  
Tail Length ◽  
Tca Cycle ◽  
Mouse Cell ◽  
Mrna Abundance ◽  
Mouse Tissues ◽  
Post Transcriptional Regulation ◽  
Genome Activation

AbstractMitochondria are responsible for producing a cell’s energy and play a central role in many metabolic tasks, as well as signaling transduction and cell death1. Mitochondria dysfunctions cause several human diseases and aging processes2–8. Mammalian oocytes contain far more mitochondria than somatic cells. The nuclear localization of mitochondrial tricarboxylic acid cycle (TCA) cycle enzymes, which normally localize in the mitochondria, is critical for zygotic genome activation (ZGA) and the oocyte-to-embryo transition (OET) in mice9. However, during the mammalian OET, the abundance and post-transcriptional regulation of mitochondrial mRNA (MT-mRNA), particularly the poly(A) tail, has never been studied. Here, we used two independent sequencing methods (PAIso-seq1 and PAIso-seq2) to describe the features of MT-mRNA in mouse cell lines, thirteen mouse tissues and during the OET in mouse, rat, pig, and humans. These features included expression abundance, poly(A) tail length, and non-A residues in poly(A) tails. Unlike nuclear mRNA, we discovered that MT-mRNA has a stable distribution pattern of poly(A) tail length in different cell lines, across tissues, and during mammalian OET. MT-mRNA possesses non-A residues in the poly(A) tail (non-A residues hereafter), which change slightly across tissues and during the OET. We also found that the abundance of MT-mRNA varies substantially across tissues, increases during the OET, and increases along major ZGA in mice, rats, pigs, and humans. These findings provide insights into changes in MT-mRNA abundance and poly(A) tail during the mammalian OET and provide a resource for future studies on the posttranscriptional regulation of mitochondrial transcripts.

scholarly journals Dynamics of poly(A) tail length and non-A residues during the human oocyte-to-embryo transition

2021 ◽  
Author(s):  
Yusheng Liu ◽  
Keliang Wu ◽  
Fanghong Shao ◽  
Hu Nie ◽  
Jingye Zhang ◽  
...  
Keyword(s):  
Single Gene ◽  
Tail Length ◽  
Human Embryos ◽  
Human Oocyte ◽  
Human Oocytes ◽  
Maternal Mrna ◽  
Maternal Transcripts ◽  
Low Sensitivity ◽  
Post Transcriptional Regulation

AbstractPoly(A) tail-mediated post-transcriptional regulation of maternal mRNA has been shown to be vital in the oocyte-to-embryo transition (OET) in flies, fish, frogs, and mice1–8. However, nothing is known about poly(A) tail dynamics for even a single gene during the human OET, because of the limited availability of human oocytes and embryos in combination with the low sensitivity of previous methods. Here, we systematically profiled the transcriptome-wide mRNA poly(A) tails in human oocytes at the germ-vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as pre-implantation embryos at the 1-cell (1C), 2-cell (2C), 4-cell (4C), 8-cell (8C), morula (MO), and blastocyst (BL) stages using single-oocyte/embryo PAIso-seq1 and PAIso-seq2 methods. We show that poly(A) tail length is highly dynamic during the OET, with BTG4 responsible for global deadenylation. Moreover, we reveal that non-A residues occur primarily in poly(A) tails of maternal RNA, which begin to increase at the MI stage, become highly abundant after fertilization (with U residues occurring in about two thirds, G residues in about one third, and C residues in about one fifth of mRNAs), and decline at the 8C stage. Importantly, we reveal that TUT4/7 can add U residues to deadenylated mRNA, which can then be re- polyadenylated to produce 5′-end and internal U residues. In addition, the re- polyadenylated mRNA can be stabilized through the addition of G residues by TENT4A/B. Finally, we demonstrate that U residues in poly(A) tails mark the maternal transcripts for quicker degradation in 8C human embryos compared to those without U residues. Together, our results not only reveal the dynamics of poly(A) tail length and non-A residues, but also provide mechanistic insights into the regulation of the length and the role of non-A residues during human OET. These findings further scientific understanding and open a new door for studying the human OET.

scholarly journals Re-polyadenylation occurs predominantly on maternal mRNA degradation intermediates during mammalian oocyte-to-embryo transition

2021 ◽  
Author(s):  
Yusheng Liu ◽  
Yiwei Zhang ◽  
Hu Nie ◽  
Zhonghua Liu ◽  
Jiaqiang Wang ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Mrna Degradation ◽  
Mammalian Oocyte ◽  
Maternal Mrna ◽  
Early Embryos ◽  
Specific Regulation ◽  
And Function ◽  
Post Transcriptional Regulation ◽  
Degradation Intermediates ◽  
Polyadenylated Mrna

The nascent mRNA transcribed in the nucleus is cleaved and polyadenylated before it is transported to the cytoplasm for translation. Polyadenylation can also occur in the cytoplasm for post-transcriptional regulation, especially in neurons, oocytes and early embryos. Recently, we revealed transcriptome-wide maternal mRNA cytoplasmic re-polyadenylation during the mammalian oocyte-to-embryo transition (OET). However, the mechanism of re-polyadenylation during mammalian OET, including the sites to be re-polyadenylated and the enzymes involved, is still poorly understood. Here, by analyzing the PAIso-seq1 and PAIso-seq2 poly(A) inclusive transcriptome data during OET in mice, rats, pigs, and humans, we reveal conserved re-polyadenylation of mRNA degradation intermediates. These re-polyadenylated mRNA degradation intermediates account for over half of the polyadenylated mRNA during OET in all four species. We find that mRNA degradation intermediates for re-polyadenylation are generated through Btg4-mediated deadenylation in both mouse and human. Interestingly, the poly(A) tails on the re-polyadenylated mRNA degradation intermediates are of different lengths and contain different levels of non-A residues compared to regular polyadenylation sites, suggesting specific regulation and function of these poly(A) tails in mammalian OET. Together, our findings reveal the maternal mRNA degradation intermediates as substrates for conserved cytoplasmic dominant re-polyadenylation during mammalian OET, and uncover the mechanism of production of these mRNA degradation intermediates. These findings provide new insights into mRNA post-transcriptional regulation, and a new direction for the study of mammalian OET.

Oocyte Maternal mRNA Translation and Developmental Competence: A Genome-Wide Analysis.

2012 ◽  
Vol 87 (Suppl_1) ◽  
pp. 88-88 ◽  
Author(s):  
Marco Conti ◽  
Jing Chen ◽  
Fang Xie ◽  
Chi-Jen Lin ◽  
Kathleen Horner
Keyword(s):  
Mrna Translation ◽  
Developmental Competence ◽  
Genome Wide Analysis ◽  
Maternal Mrna ◽  
Genome Wide ◽  
A Genome
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