DAZL and CPEB1 regulate mRNA translation synergistically during oocyte maturation

Martins, Joao P. Sousa; Liu, Xueqing; Oke, Ashwini; Arora, Ritu; Franciosi, Federica; Viville, Stéphane; Laird, Diana J.; Fung, Jennifer C.; Conti, Marco

doi:10.1242/jcs.179218

Cited by 82 publications

(97 citation statements)

References 45 publications

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“…The availability of a conditional DAZL is also highly expressed in ovary, in oocytes of all stages (see Supplementary Fig. S3A) (22,35). Full body Dazl knockout led to an ovary without any follicles, similar to the previously reported knockout (see Supplementary Fig.…”

Section: Removal Of Dazl In Gonocytes Spermatogonia and Spermatocytesupporting

confidence: 81%

“…Given the requirement of DAZL throughout spermatogenesis, we next examined the mechanism of DAZL action at the molecular level, specifically, how it controls protein expression of its targets. Several previous reports have suggested DAZL played important roles as an enhancer of mRNA translation in germ cell development (33)(34)(35).…”

Section: Dazl Is Required For Translation Of Its Targets Mrnas and Inmentioning

confidence: 95%

“…Among 11 testicular targets mRNA, Reynolds et al showed that translation of two of them (Vasa and Sycp3) could be enhanced by DAZL based on a few survived germ cells in Dazl knockout mouse testes (33,34). Polysome profiling of mouse oocytes at different stages revealed extensive translational regulation, DAZL was proposed to be one of the key translational regulators working synergistically with CPEB (22,35).…”

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confidence: 99%

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DAZL is a master translational regulator of murine spermatogenesis

Liang

Yang

et al. 2018

Preprint

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Expression of DAZ-like (DAZL) is a hallmark of vertebrate germ cells and essential for embryonic germ cell development and differentiation, yetgametogenic function of DAZL has not been fully characterized with most of its in vivo direct targets unknown. We showed that postnatal stage-specific deletion of Dazl in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells (SSCs), meiotic arrest and spermatid arrest respectively. Using the genome-wide HITS-CLIP and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at 3' UnTranslated Region (3' UTR) and interacted with translation proteins including PABP. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts were significantly decreased, resulting in drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is

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Section: Removal Of Dazl In Gonocytes Spermatogonia and Spermatocytesupporting

confidence: 81%

Section: Dazl Is Required For Translation Of Its Targets Mrnas and Inmentioning

confidence: 95%

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confidence: 99%

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DAZL is a master translational regulator of murine spermatogenesis

Liang

Yang

et al. 2018

Preprint

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“…All animals used were of the C57BL/6J inbred strain. C57BL/6-Zp3cre-Rpl22tm1.1Psam (Zp3-Cre T RiboTag) mice were obtained from Jackson Laboratories and bred as previously described 20 . CPEB1-targeted mice were a gift from Raúl Méndez and colleagues 45 and bred in our laboratory.…”

Section: Animalsmentioning

confidence: 99%

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

Luong

Daldello

Rajkovic³

et al. 2019

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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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“…DAZL interacts with the 3' UTRs of factors that contribute to multiple stages of 5 spermatogenesis, but it is not clear what transcripts DAZL targets in specific spermatogenic cell types because these targets have been identified in either cultured primordial germ cell-like cells (Chen et al, 2014), ovaries (Rosario et al, 2017), or whole testes containing many stages of spermatogenesis (Chen et al, 2014;Li et al, 2019;Zagore et al, 2018). DAZL functions as a translational enhancer within the oocyte (Collier et al, 2005;Reynolds et al, 2005;Reynolds et 10 al., 2007;Sousa Martins et al, 2016). However, during spermatogenesis, and particularly in spermatogonia, there is conflicting evidence whether DAZL regulates translation (Li et al, 2019;Reynolds et al, 2005;Reynolds et al, 2007) or RNA stability (Zagore et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial progenitors

Mikedis

Fan

Nicholls

et al. 2020

Preprint

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Fertility across metazoa requires the germline-specific DAZ family of RNA-binding proteins.Here we examine whether DAZL directly regulates progenitor spermatogonia using a conditional genetic mouse model and in vivo biochemical approaches combined with chemical synchronization of spermatogenesis. We find that the absence of Dazl impairs both expansion 5 and differentiation of the spermatogonial progenitor population. In undifferentiated spermatogonia, DAZL binds the 3' UTRs of ~2,500 protein-coding genes. Some targets are known regulators of spermatogonial proliferation and differentiation while others are broadly expressed, dosage-sensitive factors that control transcription and RNA metabolism. DAZL binds 3' UTR sites conserved across vertebrates at a UGUU(U/A) motif. By assessing ribosome 10 occupancy in undifferentiated spermatogonia, we find that DAZL increases translation of its targets. In total, DAZL orchestrates a broad translational program that amplifies protein levels of key spermatogonial and gene regulatory factors to promote the expansion and differentiation of progenitor spermatogonia.2

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DAZL and CPEB1 regulate mRNA translation synergistically during oocyte maturation

Cited by 82 publications

References 45 publications

DAZL is a master translational regulator of murine spermatogenesis

DAZL is a master translational regulator of murine spermatogenesis

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

DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial progenitors

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