scholarly journals Chromatin-Associated Protein Sugp2 Involved in mRNA Alternative Splicing During Mouse Spermatogenesis

2021 ◽  
Vol 8 ◽  
Author(s):  
Junfeng Zhan ◽  
Jianbo Li ◽  
Yuerong Wu ◽  
Panfeng Wu ◽  
Ziqi Yu ◽  
...  

Mammalian spermatogenesis is a highly ordered process that is determined by chromatin-associated moderators which still remain poorly understood. Through a multi-control group proteomics strategy, we confirmed that Sugp2 was a chromatin-associated candidate protein, and its signal arose along spermatogenesis. The expression results showed that Sugp2, which is mainly expressed in the testis, had two transcripts, encoding one protein. During spermatogenesis, Sugp2 was enriched in the nucleus of male germ cells. With the depletion of Sugp2 by CRISPER-Cas9 technology, we found that Sugp2 controlled a network of genes on metal ion and ATP binding, suggesting that alternative splicing regulation by Sugp2 is involved in cellular ion and energy metabolism during spermatogenesis, while it had a little effect on meiotic progression and male fertility. Collectively, these data demonstrated that, as a chromatin-associated protein, Sugp2 mediated the alternative splicing regulatory network during spermatogenesis.

Author(s):  
Rui Wu ◽  
Junfeng Zhan ◽  
Bo Zheng ◽  
Zhen Chen ◽  
Jianbo Li ◽  
...  

SYMPK is a scaffold protein that supports polyadenylation machinery assembly on nascent transcripts and is also involved in alternative splicing in some mammalian somatic cells. However, the role of SYMPK in germ cells remains unknown. Here, we report that SYMPK is highly expressed in male germ cells, and germ cell-specific knockout (cKO) of Sympk in mouse leads to male infertility. Sympk cKODdx4–cre mice showed reduced spermatogonia at P4 and almost no germ cells at P18. Sympk cKOStra8–Cre spermatocytes exhibit defects in homologous chromosome synapsis, DNA double-strand break (DSB) repair, and meiotic recombination. RNA-Seq analyses reveal that SYMPK is associated with alternative splicing, besides regulating the expressions of many genes in spermatogenic cells. Importantly, Sympk deletion results in abnormal alternative splicing and a decreased expression of Sun1. Taken together, our results demonstrate that SYMPK is pivotal for meiotic progression by regulating pre-mRNA alternative splicing in male germ cells.


PLoS Genetics ◽  
2011 ◽  
Vol 7 (7) ◽  
pp. e1002157 ◽  
Author(s):  
Michelle L. Churchman ◽  
Ignasi Roig ◽  
Maria Jasin ◽  
Scott Keeney ◽  
Charles J. Sherr

2011 ◽  
Vol 39 (12) ◽  
pp. 4961-4974 ◽  
Author(s):  
Maria Paola Paronetto ◽  
Valeria Messina ◽  
Marco Barchi ◽  
Raffaele Geremia ◽  
Stéphane Richard ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2266
Author(s):  
Constanza Tapia Contreras ◽  
Sigrid Hoyer-Fender

The sperm flagellum is essential for the transport of the genetic material toward the oocyte and thus the transmission of the genetic information to the next generation. During the haploid phase of spermatogenesis, i.e., spermiogenesis, a morphological and molecular restructuring of the male germ cell, the round spermatid, takes place that includes the silencing and compaction of the nucleus, the formation of the acrosomal vesicle from the Golgi apparatus, the formation of the sperm tail, and, finally, the shedding of excessive cytoplasm. Sperm tail formation starts in the round spermatid stage when the pair of centrioles moves toward the posterior pole of the nucleus. The sperm tail, eventually, becomes located opposed to the acrosomal vesicle, which develops at the anterior pole of the nucleus. The centriole pair tightly attaches to the nucleus, forming a nuclear membrane indentation. An articular structure is formed around the centriole pair known as the connecting piece, situated in the neck region and linking the sperm head to the tail, also named the head-to-tail coupling apparatus or, in short, HTCA. Finally, the sperm tail grows out from the distal centriole that is now transformed into the basal body of the flagellum. However, a centriole pair is found in nearly all cells of the body. In somatic cells, it accumulates a large mass of proteins, the pericentriolar material (PCM), that together constitute the centrosome, which is the main microtubule-organizing center of the cell, essential not only for the structuring of the cytoskeleton and the overall cellular organization but also for mitotic spindle formation and chromosome segregation. However, in post-mitotic (G1 or G0) cells, the centrosome is transformed into the basal body. In this case, one of the centrioles, which is always the oldest or mother centriole, grows the axoneme of a cilium. Most cells of the body carry a single cilium known as the primary cilium that serves as an antenna sensing the cell’s environment. Besides, specialized cells develop multiple motile cilia differing in substructure from the immotile primary cilia that are essential in moving fluids or cargos over the cellular surface. Impairment of cilia formation causes numerous severe syndromes that are collectively subsumed as ciliopathies. This comparative overview serves to illustrate the molecular mechanisms of basal body formation, their similarities, and dissimilarities, in somatic versus male germ cells, by discussing the involved proteins/genes and their expression, localization, and function. The review, thus, aimed to provide a deeper knowledge of the molecular players that is essential for the expansion of clinical diagnostics and treatment of male fertility disorders.


Development ◽  
1990 ◽  
Vol 109 (1) ◽  
pp. 37-40
Author(s):  
S. Dolci ◽  
M. De Felici

The influence of somatic environment on the onset and progression of meiosis in fetal germ cells was studied in chimeric gonads produced in vitro by dissociation-reaggregation experiments. Germ cells isolated from testes or ovaries of 11.5-13.5 days post coitum (dpc) CD-1 mouse embryos were loaded with the fluorescent supravital dye 5–6 carboxyfluorescein diacetate succinimyl ester (CFSE) and mixed with a cell suspension obtained by trypsin-EDTA treatment of gonads of various ages and of the same or opposite sex. Whereas 11.5 dpc donor germ cells appeared unable to survive in the chimeric gonads obtained, about 76% of the CFSE-labeled female germ cells obtained from 12.5 dpc donor embryos (premeiotic germ cells) found viable within host ovarian tissues showed a meiotic nucleus. In contrast, a smaller number (about 19%) were in meiosis in chimeric testes. None or very few of donor male germ cells entered meiosis in testes or ovarian host tissues. Aggregation of meiotic 13.5 dpc female germ cells with testis tissues from 13.5 to 14.5 dpc embryos resulted in inhibition of meiotic progression and pyknosis in most donor germ cells. These results support the existence of a meiosis-preventing substance or a factor causing oocyte degeneration in the fetal mouse testis, but not of a meiosis-inducing substance in the fetal ovary.


Reproduction ◽  
2017 ◽  
Vol 154 (6) ◽  
pp. 755-764 ◽  
Author(s):  
Tomoyuki Muroi ◽  
Yuri Matsushima ◽  
Ryota Kanamori ◽  
Hikari Inoue ◽  
Wataru Fujii ◽  
...  

G-protein-coupled receptors (GPCRs) participate in diverse physiological functions and are promising targets for drug discovery. However, there are still over 140 orphan GPCRs whose functions remain to be elucidated.Gpr62is one of the orphan GPCRs that is expressed in the rat and human brain. In this study, we found thatGpr62is also expressed in male germ cells in mice, and its expression increases along with sperm differentiation. GPR62 lacks the BBXXB and DRY motifs, which are conserved across many GPCRs, and it was able to induce cAMP signaling in the absence of a ligand. These structural and functional features are conserved among mammals, and the mutant analysis of GPR62 has revealed that lacking of these motifs is involved in the constitutive activity. We also found that GPR62 can homooligomerize, but it is not sufficient for its constitutive activity. We further investigated its physiological function by usingGpr62knockout (Gpr62−/−) mice.Gpr62−/−mice were born normally and did not show any abnormality in growth and behavior. In addition, both male and femaleGp62−/−mice were fertile, and the differentiation and motility of spermatozoa were normal. We also found thatGpr61, the gene most similar toGpr62in the GPCR family shows a constitutive activity and an expression pattern similar to those ofGpr62. Our results suggest that GPR62 constitutively activates the cAMP pathway in male germ cells but is dispensable for male fertility, which is probably due to its functional redundancy with GPR61.


2020 ◽  
Vol 35 (9) ◽  
pp. 1983-1990 ◽  
Author(s):  
Henrike Krenz ◽  
Jörg Gromoll ◽  
Thomas Darde ◽  
Frederic Chalmel ◽  
Martin Dugas ◽  
...  

Abstract STUDY QUESTION How can one design and implement a system that provides a comprehensive overview of research results in the field of epi-/genetics of male infertility and germ cells? SUMMARY ANSWER Working at the interface of literature search engines and raw data repositories, the newly developed Male Fertility Gene Atlas (MFGA) provides a system that can represent aggregated results from scientific publications in a standardized way and perform advanced searches, for example based on the conditions (phenotypes) and genes related to male infertility. WHAT IS KNOWN ALREADY PubMed and Google Scholar are established search engines for research literature. Additionally, repositories like Gene Expression Omnibus and Sequence Read Archive provide access to raw data. Selected processed data can be accessed by visualization tools like the ReproGenomics Viewer. STUDY DESIGN, SIZE, DURATION The MFGA was developed in a time frame of 18 months under a rapid prototyping approach. PARTICIPANTS/MATERIALS, SETTING, METHODS In the context of the Clinical Research Unit ‘Male Germ Cells’ (CRU326), a group of around 50 domain experts in the fields of male infertility and germ cells helped to develop the requirements engineering and feedback loops. They provided a set of 39 representative and heterogeneous publications to establish a basis for the system requirements. MAIN RESULTS AND THE ROLE OF CHANCE The MFGA is freely available online at https://mfga.uni-muenster.de. To date, it contains 115 data sets corresponding to 54 manually curated publications and provides an advanced search function based on study conditions, meta-information and genes, whereby it returns the publications’ exact tables and figures that fit the search request as well as a list of the most frequently investigated genes in the result set. Currently, study data for 31 different tissue types, 32 different cell types and 20 conditions are available. Also, ∼8000 and ∼1000 distinct genes have been found to be mentioned in at least 10 and 15 of the publications, respectively. LARGE SCALE DATA Not applicable because no novel data were produced. LIMITATIONS, REASONS FOR CAUTION For the most part, the content of the system currently includes the selected publications from the development process. However, a structured process for the prospective literature search and inclusion into the MFGA has been defined and is currently implemented. WIDER IMPLICATIONS OF THE FINDINGS The technical implementation of the MFGA allows for accommodating a wide range of heterogeneous data from aggregated research results. This implementation can be transferred to other diseases to establish comparable systems and generally support research in the medical field. STUDY FUNDING/COMPETING INTEREST(S) This work was carried out within the frame of the German Research Foundation (DFG) Clinical Research Unit ‘Male Germ Cells: from Genes to Function’ (CRU326). The authors declare no conflicts of interest.


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