DAZL is a master translational regulator of murine spermatogenesis

Li, Haixin; Liang, Zhenjie; Yang, Jian; Wang, Dan; Wang, Hanben; Zhu, Mengyi; Geng, Baobao; Xu, Eugene Yujun

doi:10.1093/nsr/nwy163

Cited by 89 publications

(90 citation statements)

References 59 publications

(94 reference statements)

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“…Together with DAZ and BOULE, they consist of a human fertility family, which is necessary for gametogenesis in worms, flies, mice, and humans [98]. DAZL co-localizes with MIWI in pachytene spermatocytes and exhibits higher expression levels in the cytoplasm of pachytene spermatocytes [85,86]. The global knockout of the Dazl gene leads to severe disruption of testicular histology with a nearly complete loss of germ cells beyond the spermatogonial stage [85].…”

Section: Dazlmentioning

confidence: 99%

Section: Dazlmentioning

confidence: 99%

“…Dazl predominantly functions directly as a positive post-transcriptional regulator through 3'-UTR interactions via the motif UGUU, thereby controlling a network of specific genes required for germ cell survival [86,102]. Stage-specific deletion of Dazl in gonocytes (Vasa-Cre mediated, VKO), spermatogonia (Stra8-Cre mediated, SKO), and spermatocytes (Hspa2-Cre mediated, HKO) all result in complete male sterility [86]. Characterization by an absence of germ cells in VKO due to a significant decrease of spermatogonia-associated DAZL target protein expression, zygotene stage arrest in SKO due to the disrupted assembly of the synaptonemal complex and DNA repair, and round spermatid stage arrest in HKO mice, confirm its requirement at these three stages of spermatogenesis by recruiting PABP to target DAZL mRNAs to regulate their translation [86].…”

Section: Dazlmentioning

confidence: 99%

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Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Wang

Guo

et al. 2020

Cells

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Multiple specific granular structures are present in the cytoplasm of germ cells, termed nuage, which are electron-dense, non-membranous, close to mitochondria and/or nuclei, variant size yielding to different compartments harboring different components, including intermitochondrial cement (IMC), piP-body, and chromatoid body (CB). Since mitochondria exhibit different morphology and topographical arrangements to accommodate specific needs during spermatogenesis, the distribution of mitochondria-associated nuage is also dynamic. The most relevant nuage structure with mitochondria is IMC, also called pi-body, present in prospermatogonia, spermatogonia, and spermatocytes. IMC is primarily enriched with various Piwi-interacting RNA (piRNA) proteins and mainly functions as piRNA biogenesis, transposon silencing, mRNA translation, and mitochondria fusion. Importantly, our previous work reported that mitochondria-associated ER membranes (MAMs) are abundant in spermatogenic cells and contain many crucial proteins associated with the piRNA pathway. Provocatively, IMC functionally communicates with other nuage structures, such as piP-body, to perform its complex functions in spermatogenesis. Although little is known about the formation of both IMC and MAMs, its distinctive characters have attracted considerable attention. Here, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We discuss the roles of the structural components in spermatogenesis and piRNA biogenesis, which provide new insights into mitochondria-associated germinal structures in germ cell development and male reproduction. Cells 2020, 9, 399 2 of 20Mitochondria-associated ER membranes (MAMs) are tight structural contacts, also named as MERCs (mitochondria-ER contacts);~20% of the mitochondrial surface are jointly opposing and contact directly with the ER, yielding to approximately 10 and 30 nm in distance [4,5]. MAMs participate in several cellular signaling pathways, including calcium transmission, phospholipid exchange, intracellular trafficking, autophagy, ER stress, mitochondrial biogenesis, and inflammasome formation. Disturbances to MAMs lead to neurodegenerative diseases and cancer [6,7]. Our previous work reported that MAMs are abundant in both human and mouse spermatogenic cells, and contain many crucial proteins that are associated with the Piwi-interacting RNA (piRNA) pathway [8]. However, the functions of MAMs are still mysterious in spermatogenesis.In this review, we review the insights gained from studying the structural components of mitochondria-associated germinal structures, including IMC, CB, and MAMs, which are pivotal structures to ensure genome integrity and male fertility. We summarize the ultra-structure of IMC and MAMs in mouse spermatocyte, as shown in Figure 1A. We also discuss the roles of the structural components in piRNA biogenesis and propose that further s...

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Section: Dazlmentioning

confidence: 99%

Section: Dazlmentioning

confidence: 99%

Section: Dazlmentioning

confidence: 99%

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Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Wang

Guo

et al. 2020

Cells

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“…Most recently, we demonstrated that TAF4b is a critical regulator of female meiosis I in the mouse [11]. Taf4b mRNA expression is also highly correlated with the expression of many important germline genes during human fetal ovary development, such as Deleted in Azoospermia-like (Dazl), which encodes a germ cell-specific RNA-binding protein that promotes translation and/or prevents the degradation of its target mRNAs [11][12][13]. In female mice as early as E13.5, when germ cells initiate meiosis, Taf4b-deficiency results in reduced expression of meiotic transcripts, including Stimulated by Retinoic Acid 8 (Stra8), which is a master regulator of meiosis [14].…”

Section: Introductionmentioning

confidence: 99%

Dynamic and regulated TAF gene expression during mouse embryonic germ cell development

et al. 2020

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All sequencing data are available from NCBI GEO https://www.ncbi.nlm. nih.gov/geo under accession number GSE139005 and NCBI SRA (https://www.ncbi.nlm.nih.gov/sra) under accession number SRP226023. The RNAseq data used in this research is from the following accession numbers: the mouse data from E9.5 to E18.5 in female and male sorted Oct4-EGFP gonads used for Figs 1, 2, 4, 5, and 10 was obtained through ArrayExpress: E-MTAB-4616; the human data comparing female germ cells versus somatic cells used for Fig 3A was obtained through sperm. Here, we analyzed data from public repositories and isolated these developing cells to examine their gene expression patterns throughout embryonic development. Together these data suggest that the dynamic expression of Taf4b and other TFIID family members are dependent on the well-established reproductive cell regulators Dazl and Stra8. This understanding of Taf4b gene expression and regulation in mouse reproductive cell development is likely conserved during development of human cells and offers novel insights into the interconnectedness of the factors that govern the formation of healthy eggs and sperm.

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“…However, additional studies in PGCs suggest a repressive function for this RBP in the control of fetal gonad development and embryonic stem cell in the mouse 17,18 . Moreover, depletion of DAZL during postnatal spermatogenesis has been associated with mRNA destabilization 19 or translational activation 20 .…”

mentioning

confidence: 99%

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

et al. 2020

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Deleted in azoospermia-like (DAZL) is an RNA-binding protein critical for gamete development. In full-grown oocytes, the DAZL protein increases 4-fold during reentry into the meiotic cell cycle. Here, we have investigated the functional significance of this accumulation at a genome-wide level. Depletion of DAZL causes a block in maturation and widespread disruption in the pattern of ribosome loading on maternal transcripts. In addition to decreased translation, DAZL depletion also causes translational activation of a distinct subset of mRNAs both in quiescent and maturing oocytes, a function recapitulated with YFP-3′UTR reporters. DAZL binds to mRNAs whose translation is both repressed and activated during maturation. Injection of recombinant DAZL protein in DAZL-depleted oocytes rescues the translation and maturation to MII. Mutagenesis of putative DAZL-binding sites in these mRNAs mimics the effect of DAZL depletion. These findings demonstrate that DAZL regulates translation of maternal mRNAs, functioning both as the translational repressor and activator during oocyte maturation.

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DAZL is a master translational regulator of murine spermatogenesis

Cited by 89 publications

References 59 publications

Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Mitochondria Associated Germinal Structures in Spermatogenesis: piRNA Pathway Regulation and Beyond

Dynamic and regulated TAF gene expression during mouse embryonic germ cell development

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

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