scholarly journals Rapid gene evolution in an ancient post-transcriptional and translational regulatory system compensates for meiotic X chromosomal inactivation

2021 ◽  
Author(s):  
Shengqian Xia ◽  
Iuri M. Ventura ◽  
Andreas Blaha ◽  
Annamaria Sgromo ◽  
Shuaibo Han ◽  
...  
Keyword(s):  
Male Fertility ◽  
Translational Regulation ◽  
Gene Evolution ◽  
Regulatory System ◽  
Biological Processes ◽  
Duplicated Genes ◽  
Mrna Regulation ◽  
A Subunit ◽  
And Function ◽  
Transcriptional And Translational Regulation

SUMMARYIt is conventionally assumed that conserved pathways evolve slowly with little participation of gene evolution. Nevertheless, it has been recently observed that young genes can take over fundamental functions in essential biological processes, for example, development and reproduction. It is unclear how newly duplicated genes are integrated into ancestral networks and reshape the conserved pathways of important functions. Here, we investigated origination and function of two autosomal genes that evolved recently in Drosophila: Poseidon and Zeus, which were created by RNA-based duplications from the X-linked CAF40, a subunit of the conserved CCR4-NOT deadenylase complex involved in post-transcriptional and translational regulation. Knockdown and knockout assays show that the two genes quickly evolved critically important functions in viability and male fertility. Moreover, our transcriptome analysis demonstrates that the three genes have a broad and distinct effect in the expression of hundreds of genes, with almost half of the differentially expressed genes being perturbed exclusively by one paralog, but not the others. Co-immunoprecipitation and tethering assays show that the CAF40 paralog Poseidon maintains the ability to interact with the CCR4-NOT deadenylase complex and might act in post-transcriptional mRNA regulation. The rapid gene evolution in the ancient post-transcriptional and translational regulatory system may be driven by evolution of sex chromosomes to compensate for the meiotic X chromosomal inactivation (MXCI) in Drosophila.

Comparative effects of Orchis anatolica vs. the red Korean Panax ginseng treatments on testicular structure and function of adult male mice

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Nabil A. Khouri ◽  
Haytham M. Daradka ◽  
Mohammed Z. Allouh ◽  
Ahmad S. Alkofahi
Keyword(s):  
Panax Ginseng ◽  
Male Fertility ◽  
Virgin Female ◽  
Reproductive Organs ◽  
Serum Markers ◽  
Structure And Function ◽  
Control Group ◽  
Male Mice ◽  
Fertility Potential ◽  
And Function

Abstract: The effects of: Both plants were administered orally to two separate mice groups at a dose of 800 mg/kg/day for 35 days and compared with control group. After treatment, 5 mice of each group were sacrificed and total mice weights, reproductive organs’ weights, spermatogenesis, and androgenic serum markers were investigated. The remaining mice from all groups were allowed to mate with virgin female mice to explore male fertility potential.: Results indicated that body and organs’ weights were increased significantly in mice treated with: We can conclude that

scholarly journals Deficiency of the onco-miRNA cluster, miR-106b∼25, causes oligozoospermia and the cooperative action of miR-106b∼25 and miR-17∼92 is required to maintain male fertility

2020 ◽  
Vol 26 (6) ◽  
pp. 389-401
Author(s):  
Alicia Hurtado ◽  
Rogelio Palomino ◽  
Ina Georg ◽  
Miguel Lao ◽  
Francisca M Real ◽  
...  
Keyword(s):  
Male Fertility ◽  
Molecular Mechanisms ◽  
Mirna Cluster ◽  
Knock Out ◽  
Cooperative Action ◽  
Mouse Mutants ◽  
New Genes ◽  
Mirna Clusters ◽  
Testicular Histology ◽  
And Function

Abstract The identification of new genes involved in sexual development and gonadal function as potential candidates causing male infertility is important for both diagnostic and therapeutic purposes. Deficiency of the onco-miRNA cluster miR-17∼92 has been shown to disrupt spermatogenesis, whereas mutations in its paralog cluster, miR-106b∼25, that is expressed in the same cells, were reported to have no effect on testis development and function. The aim of this work is to determine the role of these two miRNA clusters in spermatogenesis and male fertility. For this, we analyzed miR-106b∼25 and miR-17∼92 single and double mouse mutants and compared them to control mice. We found that miR-106b∼25 knock out testes show reduced size, oligozoospermia and altered spermatogenesis. Transcriptomic analysis showed that multiple molecular pathways are deregulated in these mutant testes. Nevertheless, mutant males conserved normal fertility even when early spermatogenesis and other functions were disrupted. In contrast, miR-17∼92+/−; miR-106b∼25−/− double mutants showed severely disrupted testicular histology and significantly reduced fertility. Our results indicate that miR-106b∼25 and miR-17∼92 ensure accurate gene expression levels in the adult testis, keeping them within the required thresholds. They play a crucial role in testis homeostasis and are required to maintain male fertility. Hence, we have identified new candidate genetic factors to be screened in the molecular diagnosis of human males with reproductive disorders. Finally, considering the well-known oncogenic nature of these two clusters and the fact that patients with reduced fertility are more prone to testicular cancer, our results might also help to elucidate the molecular mechanisms linking both pathologies.

FKBP51 Modulates Hippocampal Size and Function in Post-translational Regulation of Parkin

2021 ◽  
Author(s):  
Bin Qiu ◽  
Zhaohui Zhong ◽  
Shawn Righter ◽  
Yuxue Xu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Translational Regulation ◽  
Disease Onset ◽  
Fold Increase ◽  
Knock Out ◽  
Fk506 Binding Protein ◽  
Protein Levels ◽  
And Function

Abstract FK506-binding protein 51 (encoded by Fkpb51) has been associated with stress-related mental illness. To identify its function, we studied the morphological consequences of Fkbp51 deletion. Artificial Intelligence-assist morphological analysis identified that Fkbp51 knock-out (KO) mice possess more elongated CA and DG but shorter in height in coronal section when compared to WT. Primary cultured Fkbp51 KO hippocampal neurons were shown to exhibit larger dendritic outgrowth than wild-type (WT) controls, pharmacological manipulation experiments suggest that this may occur through regulation of microtubule-associated protein. Both in vitro primary culture and in vivo labeling support that FKBP51 regulates microtubule-associated protein expression. Furthermore, in the absence of differences in mRNA expression, Fkbp51 KO hippocampus exhibited decreases in βIII-tubulin, MAP2, and Tau protein levels, but a greater than 2.5-fold increase in Parkin protein. Overexpression and knock-down FKBP51 demonstrated that FKBP51 negatively regulates Parkin in a dose-dependent and ubiquitin-mediated manner. These results indicate a potential novel post-translational regulatory of Parkin by FKBP51 and significance of their interaction on disease onset.

scholarly journals Zinc: A Necessary Ion for Mammalian Sperm Fertilization Competency

2018 ◽  
Vol 19 (12) ◽  
pp. 4097 ◽  
Author(s):  
Karl Kerns ◽  
Michal Zigo ◽  
Peter Sutovsky
Keyword(s):  
Male Fertility ◽  
Reproductive Tract ◽  
Zinc Supplementation ◽  
Female Reproductive Tract ◽  
Sperm Maturation ◽  
Cellular Mechanisms ◽  
Human Reproductive ◽  
Semen Processing ◽  
New Research ◽  
And Function

The importance of zinc for male fertility only emerged recently, being propelled in part by consumer interest in nutritional supplements containing ionic trace minerals. Here, we review the properties, biological roles and cellular mechanisms that are relevant to zinc function in the male reproductive system, survey available peer-reviewed data on nutritional zinc supplementation for fertility improvement in livestock animals and infertility therapy in men, and discuss the recently discovered signaling pathways involving zinc in sperm maturation and fertilization. Emphasis is on the zinc-interacting sperm proteome and its involvement in the regulation of sperm structure and function, from spermatogenesis and epididymal sperm maturation to sperm interactions with the female reproductive tract, capacitation, fertilization, and embryo development. Merits of dietary zinc supplementation and zinc inclusion into semen processing media are considered with livestock artificial insemination (AI) and human assisted reproductive therapy (ART) in mind. Collectively, the currently available data underline the importance of zinc ions for male fertility, which could be harnessed to improve human reproductive health and reproductive efficiency in agriculturally important livestock species. Further research will advance the field of sperm and fertilization biology, provide new research tools, and ultimately optimize semen processing procedures for human infertility therapy and livestock AI.

Tissue-specific peptide pools. Generation and function

2000 ◽  
Vol 72 (3) ◽  
pp. 355-363 ◽  
Author(s):  
Vadim T. Ivanov ◽  
Oleg N. Yatskin ◽  
Olga A. Kalinina ◽  
Marina M. Philippova ◽  
Andrei A. Karelin ◽  
...  
Keyword(s):  
Surrounding Medium ◽  
Regulatory System ◽  
Systematic Analysis ◽  
Tissue Specific ◽  
Tissue Extracts ◽  
Normal Ratio ◽  
And Function ◽  
Dying Cells ◽  
Specific Peptide

Systematic analysis of several tissue extracts for peptide components followed by bioactivity studies leads to formulation of the concept of "tissue-specific peptide pools". According to that concept the endogenous proteolysis of proteins with well-established functions, such as hemoglobin, actin, and cellular enzymes in tissues leads to formation of the sets (or pools) of bioactive peptides. The sets are tissue-specific on one hand and conservative in a given tissue at normal conditions on the other. The content and the composition of pool components are sensitive both to pathologies linked with alterations of tissue metabolism and to prolonged physiological changes. In vivo formation of fragments of functional proteins includes several consecutive proteolytic stages inside the cells and further release of bioactive compounds into the surrounding medium. The effects of pool components take place predominantly at tissue and cellular levels, their effects being related to stimulation or inhibition of cell growth, induction of cell differentiation, and death. The above-mentioned features lead to the proposal that the main in vivo function of components of tissue-specific peptides is maintenance of tissue homeostasis, i.e., the normal ratio of functional, dividing, differentiating, and dying cells of tissues. Components of tissue-specific peptide pools display several features distinguishing them from "classical" peptide hormones and neuromediators. Summarizing, a novel peptidergic regulatory system is considered.

The asialoglycoprotein receptor: relationships between structure, function, and expression

1995 ◽  
Vol 75 (3) ◽  
pp. 591-609 ◽  
Author(s):  
R. J. Stockert
Keyword(s):  
Translational Regulation ◽  
Chemotherapeutic Agents ◽  
Asialoglycoprotein Receptor ◽  
Receptor Expression ◽  
Coated Pits ◽  
Receptor Mediated Endocytosis ◽  
Intracellular Compartments ◽  
Foreign Genes ◽  
And Function ◽  
A Site

Transport of macromolecules into the cell by receptor-mediated endocytosis follows a complex series of intracellular transfers, passing through distinct environments. The asialoglycoprotein receptor is a prototype of the class of receptors that constitutively enters cells via coated pits and delivers ligand to these intracellular compartments. In addition to being a model of receptor-mediated endocytosis, the presence of the receptor on hepatocytes provides a membrane-bound active site for cell-to-cell interactions, has made possible the selective targeting of chemotherapeutic agents and foreign genes, and has also been implicated as a site mediating hepatitis B virus uptake. Regulated expression of receptor subunits and their intracellular trafficking during biosynthesis and endocytosis has provided insights into the relationship of receptor structure to its overall function. As a marker of hepatocellular differentiation, its study has uncovered a unique response to intracellular guanosine 3',5'-cyclic monophosphate and translational regulation of the receptor. In this review, an overview of these diverse findings is provided in an attempt to relate the various aspects of structure and function as they impact on receptor expression.

scholarly journals New gene discoveries in skeletal diseases with short stature

2021 ◽  
Author(s):  
Alice Costantini ◽  
Mari H Muurinen ◽  
Outi Mäkitie
Keyword(s):  
Short Stature ◽  
Molecular Mechanisms ◽  
Bone Growth ◽  
Massively Parallel Sequencing ◽  
Matrix Composition ◽  
Biological Processes ◽  
Novel Gene ◽  
Genetic Mechanisms ◽  
New Gene ◽  
And Function

In the last decade, the widespread use of massively-parallel sequencing has considerably boosted the number of novel gene discoveries in monogenic skeletal diseases with short stature. Defects in genes playing a role in the maintenance and function of the growth plate, the site of longitudinal bone growth, are a well-known cause of skeletal diseases with short stature. However, several genes involved in extracellular matrix composition or maintenance as well as genes partaking in various biological processes have also been characterized. This review aims to describe the latest genetic findings in spondyloepiphyseal and spondyloepimetaphyseal dysplasias and in some monogenic forms of isolated short stature. Strategies on how to successfully characterize novel skeletal phenotypes with short stature and genetic approaches to detect and validate novel gene-disease correlations will be discussed in detail. Finally, novel genetic mechanisms in the field of skeletal diseases, including variants affecting miRNAs and disrupting the chromatin structure, will be described. In summary, we discuss the latest gene discoveries underlying skeletal diseases with short stature and emphasize the importance of characterizing novel molecular mechanisms for genetic counseling, optimal management of the disease and for therapeutic innovations.

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