scholarly journals MFN2 interacts with Nuage-associated proteins and is essential for male germ cell development by controlling mRNA fate during spermatogenesis

Development ◽  
2021 ◽  
pp. dev.196295
Author(s):  
Xiaoli Wang ◽  
Yujiao Wen ◽  
Jin Zhang ◽  
Grace Swanson ◽  
Shuangshuang Guo ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Germ Cell ◽  
Rna Binding ◽  
Cell Development ◽  
Mitochondrial Fusion ◽  
Male Germ Cell ◽  
Germ Cell Development ◽  
Associated Proteins ◽  
Mrna Fate ◽  
Specific Mrna

Mitochondria play a critical role in spermatogenesis and are regulated by several mitochondrial fusion proteins. However, their functional importance associated with their structure formation and mRNA fate regulation during spermatogenesis remains unclear. Here, we show that Mitofusin 2 (MFN2), a mitochondrial fusion protein, interacts with Nuage-associated proteins (including MIWI, DDX4, TDRKH, and GASZ). Conditional mutation of Mfn2 in postnatal germ cells results in male sterility due to germ cell developmental defects. Moreover, MFN2 interacts with MFN1, another mitochondrial fusion protein with a high-sequence similarity to MFN2, in testes to facilitate spermatogenesis. Simultaneous mutation of Mfn1 and Mfn2 in testes causes very severe infertile phenotypes. Importantly, we show that MFN2 is enriched in polysome fractions of testes and interacts with MSY2, a germ cell-specific DNA/RNA-binding protein to control gamete-specific mRNA (such as Spata19) translational activity during spermatogenesis. Collectively, our findings demonstrate that MFN2 interacts with Nuage-associated proteins and MSY2 to regulate male germ cell development by controlling several gamete-specific mRNA fates.

scholarly journals Mitofusin2 cooperates with Nuage-associated proteins and involves mRNA translational machinery in controlling mRNA fates during spermatogenesis

2020 ◽  
Author(s):  
Xiaoli Wang ◽  
Yujiao Wen ◽  
Jin Zhang ◽  
Shuangshuang Guo ◽  
Congcong Cao ◽  
...  
Keyword(s):  
Germ Cell ◽  
Fusion Proteins ◽  
Rna Binding ◽  
Critical Role ◽  
Mrna Translation ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Translational Machinery ◽  
Associated Proteins ◽  
Specific Mrna

AbstractMitochondria play a critical role in spermatogenesis and regulated by several mitochondrial fusion proteins. Its interaction with other organelles forms several unique structures, including mitochondria-associated ER membrane (MAM) and a specific type of Nuage close to mitochondria. However, the importance of mitochondria functions and mitochondrial fusion proteins in its associated-structure formation and mRNA translation during spermatogenesis remain unclear. Here, we show that Mitofusin 2 (MFN2), a mitochondrial fusion GTPase protein, cooperates with Nuage-associated proteins, including MIWI, DDX4, TDRKH and GASZ and involves translational machinery to control the fates of gamete-specific mRNAs in spermatogenesis. Conditional mutation of Mfn2 in postnatal germ cells results in male sterility due to germ cell developmental defects characterized by disruption of mitochondrial morphology, abnormal MAMs structure, aberrant mRNA translational processes, and anomalous splicing events. Moreover, MFN2 interacts with MFN1, another mitochondrial fusion protein with high-sequence similar to MFN2, in testes to facilitate spermatogenesis. Mutation of Mfn1 and Mfn2 simultaneously in testes causes very severe infertile phenotypes. Importantly, we further show that MFN2 is enriched in polysome fractions in testes and interacts with MSY2, a germ cell-specific DNA/RNA-binding protein, and eukaryotic elongation factor 1 alpha (eEF1A) to control gamete-specific mRNA translational delay during spermatogenesis. Collectively, our findings demonstrate that MFN2 works with Nuage-associated proteins and involves translational secession to regulate gamete-specific mRNA fates. Our data reveal a novel molecular link among Mitofusins, Nuage-associated proteins, and mRNA translational processes in controlling male germ cell development.

scholarly journals Upregulated lncRNA Gm2044 inhibits male germ cell development by acting as miR-202 host gene

2019 ◽  
Vol 23 (2) ◽  
pp. 128-134 ◽  
Author(s):  
Meng Liang ◽  
Ke Hu ◽  
Chaofan He ◽  
Jinzhao Zhou ◽  
Yaping Liao
Keyword(s):  
Germ Cell ◽  
Cell Development ◽  
Host Gene ◽  
Male Germ Cell ◽  
Germ Cell Development

scholarly journals Epab and Pabpc1 Are Differentially Expressed During Male Germ Cell Development

2012 ◽  
Vol 19 (9) ◽  
pp. 911-922 ◽  
Author(s):  
Saffet Ozturk ◽  
Ozlem Guzeloglu-Kayisli ◽  
Necdet Demir ◽  
Berna Sozen ◽  
Orkan Ilbay ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Development ◽  
Differentially Expressed ◽  
Male Germ Cell ◽  
Germ Cell Development

scholarly journals Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse

PLoS Genetics ◽  
2017 ◽  
Vol 13 (11) ◽  
pp. e1007078 ◽  
Author(s):  
Jessica E. M. Dunleavy ◽  
Hidenobu Okuda ◽  
Anne E. O’Connor ◽  
D. Jo Merriner ◽  
Liza O’Donnell ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Development ◽  
Male Germ Cell ◽  
Germ Cell Development ◽  
Haploid Male

scholarly journals DMRTC2, PAX7, BRACHYURY/T and TERT Are Implicated in Male Germ Cell Development Following Curative Hormone Treatment for Cryptorchidism-Induced Infertility

Genes ◽  
2017 ◽  
Vol 8 (10) ◽  
pp. 267 ◽  
Author(s):  
Katharina Gegenschatz-Schmid ◽  
Gilvydas Verkauskas ◽  
Philippe Demougin ◽  
Vytautas Bilius ◽  
Darius Dasevicius ◽  
...  
Keyword(s):  
Germ Cell ◽  
Hormone Treatment ◽  
Cell Development ◽  
Male Germ Cell ◽  
Germ Cell Development

scholarly journals hnRNPH1 recruits PTBP2 and SRSF3 to cooperatively modulate alternative pre-mRNA splicing in germ cells and is essential for spermatogenesis and oogenesis

2021 ◽  
Author(s):  
Shuiqiao Yuan ◽  
Shenglei Feng ◽  
Jinmei Li ◽  
Hui Wen ◽  
Kuan Liu ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Germ Cell ◽  
Germ Cells ◽  
Rna Binding ◽  
Cell Development ◽  
Mrna Splicing ◽  
Conditional Knockout ◽  
Cell Junction ◽  
Germ Cell Development ◽  
Splicing Regulators

Abstract Coordinated regulation of alternative pre-mRNA splicing is essential for germ cell development. However, the molecular mechanism underlying that control alternative mRNA expression during germ cell development remains poorly understood. Herein, we showed that hnRNPH1, an RNA-binding protein, is highly expressed in the reproductive system and localized in the chromosomes of meiotic cells but excluded from the XY body in pachytene spermatocytes and recruits the splicing regulators PTBP2 and SRSF3 and cooperatively regulates the alternative splicing of the critical genes that are required for spermatogenesis. Conditional knockout Hnrnph1 in spermatogenic cells caused many abnormal splicing events that affect genes related to meiosis and communication between germ cells and Sertoli cells, characterized by asynapsis of chromosomes and impairment of germ-Sertoli communications, ultimately leading to male sterility. We further showed that hnRNPH1 could directly bind to SPO11 and recruit the splicing regulators PTBP2 and SRSF3 to regulate the alternative splicing of the target genes cooperatively. Strikingly, Hnrnph1 germline-specific mutant female mice were also infertile, and Hnrnph1-deficient oocytes exhibited a similar defective synapsis and cell-cell junction as shown in Hnrnph1-deficient male germ cells. Collectively, our data reveal an essential role for hnRNPH1 in regulating pre-mRNA splicing during spermatogenesis and oogenesis and support a molecular model whereby hnRNPH1 governs a network of alternative splicing events in germ cells via recruiting PTBP2 and SRSF3.

Dynamic changes in the subnuclear organisation of pre-mRNA splicing proteins and RBM during human germ cell development

1998 ◽  
Vol 111 (9) ◽  
pp. 1255-1265 ◽  
Author(s):  
D.J. Elliott ◽  
K. Oghene ◽  
G. Makarov ◽  
O. Makarova ◽  
T.B. Hargreave ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Biology ◽  
Rna Binding ◽  
Spatial Association ◽  
Cell Types ◽  
Cell Development ◽  
Mrna Splicing ◽  
Human Testis ◽  
Germ Cell Development ◽  
Nuclear Regions

RBM is a germ-cell-specific RNA-binding protein encoded by the Y chromosome in all mammals, implying an important and evolutionarily conserved (but as yet unidentified) function during male germ cell development. In order to address this function, we have developed new antibody reagents to immunolocalise RBM in the different cell types in the human testis. We find that RBM has a different expression profile from its closest homologue hnRNPG. Despite its ubiquitous expression in all transcriptionally active germ cell types, RBM has a complex and dynamic cell biology in human germ cells. The ratio of RBM distributed between punctate nuclear structures and the remainder of the nucleoplasm is dynamically modulated over the course of germ cell development. Moreover, pre-mRNA splicing components are targeted to the same punctate nuclear regions as RBM during the early stages of germ cell development but late in meiosis this spatial association breaks down. After meiosis, pre-mRNA splicing components are differentially targeted to a specific region of the nucleus. While pre-mRNA splicing components undergo profound spatial reorganisations during spermatogenesis, neither heterogeneous ribonucleoproteins nor the transcription factor Sp1 show either developmental spatial reorganisations or any specific co-localisation with RBM. These results suggest dynamic and possibly multiple functions for RBM in germ cell development.

Ocnus is essential for male germ cell development in Drosophila melanogaster

2018 ◽  
Vol 27 (5) ◽  
pp. 545-555 ◽  
Author(s):  
Y. Zheng ◽  
J. Bi ◽  
M.-Y. Hou ◽  
W. Shen ◽  
W. Zhang ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Germ Cell ◽  
Cell Development ◽  
Male Germ Cell ◽  
Germ Cell Development
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