BTG4 is a key regulator for maternal mRNA clearance during mouse early embryogenesis

Liu, Yusheng; Lu, Xukun; Shi, Junchao; Yu, Xingjiang; Zhang, Xiaoxin; Zhu, Kai; Yi, Zhaohong; Duan, Enkui; Li, Lei

doi:10.1093/jmcb/mjw023

Cited by 67 publications

(85 citation statements)

References 10 publications

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“…TEX19.1 protein accumulates during oocyte maturation and data in the testis indicate that this protein may be involved in the regulation of transposon expression 28, 29, 30 . Similarly, DAZL regulation of Btg4 mRNA translation has been reported by others 31, 32, 33 . In both mouse and human, Btg4 transcripts are highly enriched in the ovary and testis.…”

Section: Discussionsupporting

confidence: 78%

“…In both mouse and human, Btg4 transcripts are highly enriched in the ovary and testis. A consequence of the absence of BTG4 is a global delay in maternal mRNA degradation during the MZT 31, 32, 33, 34 . Given the involvement of BTG4 in mRNA destabilization, one would expect that DAZL depletion would induce mRNA stabilization by preventing Btg4 accumulation.…”

Section: Discussionmentioning

confidence: 99%

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The RNA binding protein DAZL functions as repressor and activator of maternal mRNA translation during oocyte maturation

Yang

Rajkovic

Daldello

et al. 2019

Preprint

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28Deleted in azoospermia like (DAZL) is an RNA-binding protein playing critical function during 29 gamete development. In fully-grown oocytes, DAZL protein is detected in prophase and levels 30 increase four to five fold during reentry into the meiotic cell cycle. Here, we have investigated the 31 functional significance of this DAZL accumulation in maturing oocytes. Oocyte depletion of DAZL 32 prevents progression to MII. This maturation block is associated with widespread disruption in the 33 pattern of maternal transcripts loading on ribosomes and their translation measured using a 34RiboTag IP/RNASeq or qPCR strategy. In addition to decreased ribosome loading of a subset of 35 transcripts, we found that DAZL depletion causes also translational activation of distinct subset of 36 mRNAs. DAZL binds to mRNAs whose translation is both repressed and activated during oocyte 37 maturation. Unexpectedly, DAZL depletion also causes increased ribosome loading of a subset 38 of mRNAs in quiescent GV-arrested oocytes. This dual role of repression and activation is 39 recapitulated by using YFP reporters including the 3'UTR of DAZL targets. Injection of 40 recombinant DAZL protein in DAZL-depleted oocytes rescues the translation of these targets as 41 well as maturation to MII. Mutagenesis of putative DAZL-binding sites in these candidate mRNAs 42 mimics the effect of DAZL depletion. These findings demonstrate that DAZL regulates translation 43 of maternal mRNAs in mature oocytes, functioning both as translational repressor and activator. 44 45 46

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

The RNA binding protein DAZL functions as repressor and activator of maternal mRNA translation during oocyte maturation

Yang

Rajkovic

Daldello

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…This gene has 5 transcripts, of which Cnot6-201and Cnot6-203 are translated into proteins and Cnot6-202, Cnot6-204, and Cnot6-205 are labeled as lincRNA. Previous work revealed that Cnot1 and Cnot3 are critical for deadenylation of maternal mRNA during mouse early embryogenesis (Ma et al, 2015;Liu et al, 2016). The expression profile showed Cnot6-201 and Cnot6-203 is overwhelming expressed product during preimplantation development (Figure 7D).…”

Section: The Identification Of Iss In Consecutive Stages Of Preimplanmentioning

confidence: 77%

Dynamic Alternative Splicing During Mouse Preimplantation Embryo Development

Xing

Yang

Liu

et al. 2020

Front. Bioeng. Biotechnol.

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The mechanism of alternative pre-mRNA splicing (AS) during preimplantation development is largely unknown. In order to capture the dynamic changes of AS occurring during embryogenesis, we carried out bioinformatics analysis based on scRNA-seq data over the time-course preimplantation development in mouse. We detected numerous previously-unreported differentially expressed genes at specific developmental stages and investigated the nature of AS at both minor and major zygotic genome activation (ZGA). The AS and differential AS atlas over preimplantation development were established. The differentially alternatively spliced genes (DASGs) are likely to be key splicing factors (SFs) during preimplantation development. We also demonstrated that there is a regulatory cascade of AS events in which some key SFs are regulated by differentially AS of their own gene transcripts. Moreover, 212 isoform switches (ISs) during preimplantation development were detected, which may be critical for decoding the mechanism of early embryogenesis. Importantly, we uncovered that zygotic AS activation (ZASA) is in conformity with ZGA and revealed that AS is coupled with transcription during preimplantation development. Our results may provide a deeper insight into the regulation of early embryogenesis.

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“…Thus, the 314 code controlling timed destabilization remains poorly understood. However, a CCR4/CNOT 315 complex that includes CNOT7/8 and BTG4 is responsible for destabilization of a subset of 316 repressed mRNAs [24][25][26] . Our RiboTag/RNA-Seq data do indicate that the machinery required for 317 mRNA destabilization/degradation is synthesized late during oocyte maturation due to delayed 318 translation of mRNAs such as Btg4, Cnot7, and Dcp1a.…”

Section: Activation Of Translation During Meiotic Maturation Is Depenmentioning

confidence: 99%

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

Luong

Daldello

Rajkovic³

et al. 2019

Preprint

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Cell development relies on elaborate changes in gene expression in order to transition 38 through different phenotypic and functional stages that ultimately lead to terminal differentiation. 39Changes in gene expression are achieved through transcriptional and post-transcriptional 40 regulations. Although transcriptional regulation is understood in considerable detail 1, 2 , much less 41 is known about the molecular machinery involved in translation regulation. 42Large oligomeric complexes involving proteins and non-coding RNAs are assembled on 43 the mRNA 3 to regulate its interaction with ribosomes, its translation rate, and its stability 4, 5 . In 44 somatic cells, numerous observations indicate that translation is intimately coupled with 45 degradation of mRNAs 5, 6 . Proteins recruited on the mRNA interact with elements located 46 throughout the length of the transcript 3, 7 . However, complexes nucleated around the 5' and 3' 47 polyadenylation element-binding protein (CPEB) is considered a master regulator of 63 polyadenylation and translation 18,19 . Much less is known about the role of CPEB in mammalian 64 oocytes. Here, we have used a genome-wide approach to investigate the role of this RNA-binding 65 protein (RBP) during the transition from quiescence to re-entry into the meiosis. Through a 66 detailed time course, we have investigated the temporal association between maternal mRNA 67 translation and the different steps involved in oocyte re-entry into and progression through the 68 meiosis. Using a RiboTag/RNA-Seq strategy, we describe a genome-wide switch in the 69 translation program of maternal mRNAs, and define new, critical functions of CPEB in the control 70 of this switch. 71 4 Results 72 Re-entry into meiosis coincides with rapid translational changes of stable mRNAs 73We have used a RiboTag/RNA-Seq strategy to characterize mRNA translation in oocytes 74 arrested at prophase I (GV) and in those undergoing meiotic maturation. (Fig. 1a). This strategy 75 has been previously validated 20, 21 and additional quality controls are reported (Supplementary 76 Fig. 1a-d). Upon meiotic resumption, there were both progressive increases and decreases in 77 ribosome loading of maternal mRNAs (Fig. 1b). By late metaphase I (MI), mRNAs were either 78 constitutively translated (n = 5580, CONSTITUTIVE), translationally repressed (n = 1092, 79 DOWN), or translationally activated (n = 871, UP) (FDR ≤ 0.05 and -1 ≥ log2(FC) (LFC) ≥ 1, 80 Supplementary Fig. 1e). Total mRNA levels remained stable up to MI and significant 81 destabilization was only detectable for 3% of maternal mRNAs at late MI ( Fig. 1b and 82 Supplementary Fig. 1f). Comparison of changes in total mRNA levels (transcriptome) to changes 83 in ribosome-associated mRNA levels (translatome) confirms this late MI destabilization (Fig. 1c), 84 which became prominent later during MII arrest, with a subset of mRNAs remaining stable even 85 if their translation was repressed. Changes in translation that initiate during MI were extended into 86 and amplified ...

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BTG4 is a key regulator for maternal mRNA clearance during mouse early embryogenesis

Cited by 67 publications

References 10 publications

The RNA binding protein DAZL functions as repressor and activator of maternal mRNA translation during oocyte maturation

The RNA binding protein DAZL functions as repressor and activator of maternal mRNA translation during oocyte maturation

Dynamic Alternative Splicing During Mouse Preimplantation Embryo Development

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

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