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.

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 Transcriptional and post-transcriptional regulation of NK cell development and function

2017 ◽  
Vol 177 ◽  
pp. 60-69 ◽  
Author(s):  
Jeffrey W. Leong ◽  
Julia A. Wagner ◽  
Aaron R. Ireland ◽  
Todd A. Fehniger
Keyword(s):  
Transcriptional Regulation ◽  
Nk Cell ◽  
Cell Development ◽  
And Function ◽  
Post Transcriptional Regulation

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 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 The Butterfly Effect of RNA Alterations on Transcriptomic Equilibrium

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1634 ◽  
Author(s):  
Ng Desi ◽  
Yvonne Tay
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Rna Processing ◽  
Cancer Development ◽  
Butterfly Effect ◽  
And Function ◽  
Post Transcriptional Regulation ◽  
The Impact ◽  
Rna Transcript

Post-transcriptional regulation plays a key role in modulating gene expression, and the perturbation of transcriptomic equilibrium has been shown to drive the development of multiple diseases including cancer. Recent studies have revealed the existence of multiple post-transcriptional processes that coordinatively regulate the expression and function of each RNA transcript. In this review, we summarize the latest research describing various mechanisms by which small alterations in RNA processing or function can potentially reshape the transcriptomic landscape, and the impact that this may have on cancer development.

scholarly journals Orb-dependent polyadenylation contributes to PLP expression and centrosome scaffold assembly

2021 ◽  
Author(s):  
Junnan Fang ◽  
Dorothy Lerit
Keyword(s):  
Transcriptional Regulation ◽  
Rna Binding ◽  
Genome Instability ◽  
Cytoplasmic Polyadenylation ◽  
Over Expression ◽  
Pericentriolar Material ◽  
And Function ◽  
Post Transcriptional Regulation ◽  
Mrna Polyadenylation

As the microtubule-organizing centers (MTOCs) of most cells, centrosomes engineer the bipolar mitotic spindle required for error-free mitosis. Drosophila Pericentrin (PCNT)-like protein (PLP) is a key centrosome component that directs formation of a pericentriolar material (PCM) scaffold required for PCM organization and MTOC function. Here, we investigate the post-transcriptional regulation of plp mRNA. We identify conserved binding sites for cytoplasmic polyadenylation element binding (CPEB) proteins within the plp 3′-untranslated region and examine the role of the CPEB ortholog, oo18 RNA-binding protein (Orb), in plp mRNA regulation. Our data show Orb biochemically interacts with plp mRNA and promotes PLP protein expression. Loss of orb, but not orb2, diminishes PLP levels in embryonic extracts. Consequently, PLP localization to centrosomes and function in PCM scaffolding is compromised in orb mutant embryos, resulting in genome instability and embryonic lethality. Moreover, we find PLP over-expression can restore centrosome scaffolding and rescue the cell division defects caused by orb depletion. Our data suggest Orb modulates PLP expression at the level of plp mRNA polyadenylation and showcases the post-transcriptional regulation of core, conserved centrosomal mRNAs as critical for centrosome function.

242 POST-TRANSCRIPTIONAL REGULATION OF JY-1 mRNA ABUNDANCE DURING THE BOVINE OOCYTE-TO-EMBRYO TRANSITION

2006 ◽  
Vol 18 (2) ◽  
pp. 229 ◽  
Author(s):  
A. Bettegowda ◽  
O. V. Patel ◽  
J. Yao ◽  
J. J. Ireland ◽  
G. W. Smith
Keyword(s):  
Transcriptional Regulation ◽  
Rna Polymerase Ii ◽  
De Novo ◽  
Early Embryogenesis ◽  
Meiotic Maturation ◽  
Total Rna ◽  
Early Embryos ◽  
Post Transcriptional Regulation ◽  
Alpha Amanitin ◽  
Time Point

Oocyte-expressed genes play key roles in folliculogenesis and early embryonic development. The function of JY-1, a novel gene specifically expressed in bovine oocytes and early embryos, is unknown. We previously reported the expression pattern of JY-1 mRNA during meiotic maturation and early embryogenesis. The objective of this study was to elucidate the post-transcriptional regulation of JY-1 mRNA during oocyte maturation and early embryogenesis. For investigation of changes in length of JY-1 transcripts during the oocyte-to-embryo transition, total RNA isolated from germinal vesicle (GV) oocytes, metaphase II (MII) oocytes, and pronucleus (PN) stage embryos (300 oocytes/embryos per time point) was subjected to Northern blot analysis. Three major JY-1 transcripts of different length (approximately 1.8 kb, 1.2 kb, and 700 bp) were detected in GV oocytes. The size of all transcripts was decreased at MII, and PN stages by approximately 100 to 200 bp. The intermediate sized transcript was predominant at GV, MII and PN stages. Based on these initial qualitative results focused solely on changes in transcript size, we then conducted more detailed quantitative studies (using real-time PCR) focused on characterization of temporal changes in abundance of polyadenylated versus total JY-1 transcripts during early development. Total RNA samples isolated from GV and MII oocytes and from embryos at PN, 2-cell, 4-cell, 8-cell, 16-cell, morula, and blastocyst stage (n = 5 pools of 10 oocytes/embryos per time point) were divided into two equal aliquots. One aliquot was reverse transcribed into cDNA with oligo dT primers for quantification of polyadenylated transcripts and the other aliquot was transcribed with random hexamers (RH) for quantification of total transcripts. Amounts of polyadenylated JY-1 mRNA decreased during meiotic maturation (P < 0.0001), were increased (P < 0.05) at the PN and 4-cell stages relative to the MII stage, and then decreased to nearly undetectable levels after the 16-cell stage of embryo development. In contrast, amount of total JY-1 transcripts gradually decreased from PN through 16-cell stages to nearly undetectable levels thereafter. To confirm that the up-regulation of polyadenylated JY-1 mRNA in early developing embryos was not due to de novo transcription, alpha-amanitin was used to block the RNA polymerase II enzyme during the window of the first (24-13 h post-fertilization) or the second (33-14 h post-fertilization) embryonic cell cycle, and embryos at the 2-cell and 4-cell stages were collected (n = 4 pools of 10 embryos per time point). No significant changes were observed in abundance of JY-1 mRNA in control versus alpha-amanitin treated embryos. We conclude that JY-1 transcripts decrease in length during meiotic maturation and that polyadenylated JY-1 mRNAs detected in early developing embryos are oocyte-derived and not due to de novo transcription in early embryos. This work was supported by the Rackham Foundation and the Michigan Agricultural Experiment Station.

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