scholarly journals AZFa Y Gene, DDX3Y, Evolved Novel Testis Transcript Variants in Primates with Proximal 3´UTR Polyadenylation for Germ Cell Specific Translation

Author(s):  
Peter H. Vogt ◽  
M-A. Rauschendorf ◽  
J. Zimmer ◽  
C. Drummer ◽  
R. Behr

Abstract Translational control is a major level of gene expression regulation in the male germ line. DDX3Y located in the AZFa region of the human Y chromosome encodes a conserved RNA helicase important for translational control at the G1-S phase of the cell cycle. In human, DDX3Y protein is expressed only in premeiotic male germ cells. In primates, DDX3Y evolved a second promoter producing novel testis-specific transcripts. Here, we show primate species-specific use of alternative polyadenylation (APA) sites for the testis-specific DDX3Y transcript variants. They have evolved first in the 3´UTRs of primate DDX3Y transcripts. A distal APA site is used for polyadenylation of DDX3Y testis transcripts in Callithrix jacchus; two proximal APAs in Macaca mulatta, in Pan trogloydates and in human. This shift corresponds with a significant increase of DDX3Y protein expression in the macaque testis and kidney tissue. In chimpanzee and human, shift to predominant use of the most proximal APA site is associated with translation of these DDX3Y transcripts in only premeiotic male germ cells. We therefore assume evolution of a positive selection process for functional DDX3Y testis transcripts in these primates to promote increase of their stability and balancing translation efficiency especially in the male germ line.

2003 ◽  
Vol 15 (6) ◽  
pp. 323 ◽  
Author(s):  
David Pei-Cheng Lin ◽  
Ming-Yu Chang ◽  
Bo-Yie Chen ◽  
Han-Hsin Chang

Research using stem cells has several applications in basic biology and clinical medicine. Recent advances in the establishment of male germ line stem cells provided researchers with the ability to identify, isolate, maintain, expand and differentiate the spermatogonia, the primitive male germ cells, as cell lines under in vitro conditions. The ability to culture and manipulate stem cell lines from male germ cells has gradually facilitated research into spermatogenesis and male infertility, to an extent beyond that facilitated by the use of somatic stem cells. After the introduction of exogenous genes, the spermatogonial cells can be transplanted into the seminiferous tubules of recipients, where the transplanted cells can contribute to the offspring. The present review concentrates on the origin, life cycle and establishment of stem cell lines from male germ cells, as well as the current status of transplantation techniques and the application of spermatogonial stem cell lines.


2002 ◽  
Vol 22 (24) ◽  
pp. 8478-8490 ◽  
Author(s):  
Hang Wang ◽  
Feng Liu ◽  
Clarke F. Millette ◽  
Daniel L. Kilpatrick

ABSTRACT Cholesterol biosynthesis in somatic cells is controlled at the transcriptional level by a homeostatic feedback pathway involving sterol regulatory element binding proteins (SREBPs). These basic helix-loop-helix (bHLH)-Zip proteins are synthesized as membrane-bound precursors, which are cleaved to form a soluble, transcriptionally active mature SREBP that regulates the promoters for genes involved in lipid synthesis. Homeostasis is conferred by sterol feedback inhibition of this maturation process. Previous work has demonstrated the expression of SREBP target genes in the male germ line, several of which are highly up-regulated during specific developmental stages. However, the role of SREBPs in the control of sterol regulatory element-containing promoters during spermatogenesis has been unclear. In particular, expression of several of these genes in male germ cells appears to be insensitive to sterols, contrary to SREBP-dependent gene regulation in somatic cells. Here, we have characterized a novel isoform of the transcription factor SREBP2, which is highly enriched in rat and mouse spermatogenic cells. This protein, SREBP2gc, is expressed in a stage-dependent fashion as a soluble, constitutively active transcription factor that is not subject to feedback control by sterols. These findings likely explain the apparent sterol-insensitive expression of lipid synthesis genes during spermatogenesis. Expression of a sterol-independent, constitutively active SREBP2gc in the male germ line may have arisen as a means to regulate SREBP target genes in specific developmental stages. This may reflect unique roles for cholesterol synthesis and other functional targets of SREBPs during spermatogenesis.


Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 911-923 ◽  
Author(s):  
A. Orr-Urtreger ◽  
A. Avivi ◽  
Y. Zimmer ◽  
D. Givol ◽  
Y. Yarden ◽  
...  

Developmental expression of the c-kit proto-oncogene, a receptor tyrosine kinase encoded by the W locus, was investigated by in situ hybridization in normal mouse embryos. Early after implantation transcripts were detectable only in the maternal placenta (6 1/2-7 1/2 days p.c.). Subsequently (8 1/2 days p.c.) numerous ectodermal (neural tube, sensory placodes) and endodermal (embryonic gut) derivatives expressed c-kit. Later transcripts were detected also in the blood islands of the yolk sac and in the embryonic liver, the main sites of embryonic hemopoiesis. Around midgestation, transcripts accumulated in the branchial pouches and also in primordial germ cells of the genital ridges. This complex pattern of expression remained characteristic also later in gestation, when c-kit was expressed in highly differentiated structures of the craniofacial area, in presumptive melanoblasts and in the CNS. In the adult ovary, maternal c-kit transcripts were detected. They were present in the oocytes of both immature and mature ovarian follicles, but not in the male germ line, where c-kit expression may be down regulated. Thus, c-kit activity is complex and appears in multiple tissues including those that also display defects in mutations at the W locus where c-kit is encoded. Correlation between W phenotypes and c-kit expression, as well as the regulation of the complex and multiple expression of polypeptide growth factors and receptors, is discussed.


2002 ◽  
Vol 115 (6) ◽  
pp. 1243-1250
Author(s):  
Ilham A. Muslimov ◽  
Yuan Lin ◽  
Michal Heller ◽  
Jürgen Brosius ◽  
Zahra Zakeri ◽  
...  

BC1 RNA, a small non-coding RNA polymerase III transcript, is selectively targeted to dendritic domains of a subset of neurons in the rodent nervous system. It has been implicated in the regulation of local protein synthesis in postsynaptic microdomains. The gene encoding BC1 RNA has been suggested to be a master gene for repetitive ID elements that are found interspersed throughout rodent genomes. A prerequisite for the generation of repetitive elements through retroposition and subsequent transmission in the germline is expression of the master gene RNA in germ cells. To test this hypothesis, we have investigated expression of BC1 RNA in murine male germ cells. We report that BC1 RNA is expressed at substantial levels in a subset of male germ cells. Results from cell fractionation experiments, developmental analysis,and northern and in situ hybridization showed that the RNA was expressed in pre-meiotic spermatogonia, with particularly high amounts in syncytial ensembles of cells that are primed for synchronous spermatogenic differentiation. BC1 RNA continued to be expressed in spermatocytes, but expression levels decreased during further spermatogenic development, and low or negligible amounts of BC1 RNA were identified in round and elongating spermatids. The combined data indicate that BC1 RNA operates in groups of interconnected germ cells, including spermatogonia, where it may function in the mediation of translational control. At the same time, the identification of BC1 RNA in germ cells provides essential support for the hypothesis that repetitive ID elements in rodent genomes arose from the BC1 RNA gene through retroposition.


2019 ◽  
Vol 20 (21) ◽  
pp. 5382
Author(s):  
Agata Swiatkowska ◽  
Mariola Dutkiewicz ◽  
Paulina Zydowicz-Machtel ◽  
Joanna Szpotkowska ◽  
Damian M. Janecki ◽  
...  

In this review, the latest research concerning the structure and function of the 5′-terminal region of p53 mRNA was discussed. Special attention was focused on defined structural motifs which are present in this region, as well as their conservation and plausible functional role in translation. It is known that the length of the 5′-terminal region and the structural environment of initiation codons can strongly modulate translation initiation. The ability of this region of p53 mRNA to bind protein factors was also described with special emphasis on general principles that govern, such RNA-protein interactions. The structural alterations within the 5′-terminal region of p53 mRNA and proteins that bind to this region have a strong impact on the rate of mRNA scanning and on translation efficiency in in vitro assays, in selected cell lines, and under stress conditions. Thus, the structural features of the 5′-terminal region of p53 mRNA seem to be very important for translation and for translation regulation mechanisms. Finally, we suggested topics that, in our opinion, should be further explored for better understanding of the mechanisms of the p53 gene expression regulation at the translational level.


2014 ◽  
Vol 20 (12) ◽  
pp. 1208-1222 ◽  
Author(s):  
Marc-Alexander Rauschendorf ◽  
Jutta Zimmer ◽  
Caroline Ohnmacht ◽  
Peter H. Vogt

1985 ◽  
Vol 5 (7) ◽  
pp. 1791-1794 ◽  
Author(s):  
C Ponzetto ◽  
D J Wolgemuth

RNA from immature mouse testes was shown to lack a low-molecular-weight c-abl transcript previously noted to be the predominant species in adult testes. The developmental pattern of appearance of this c-abl variant was determined by analyzing RNA obtained from purified populations of testicular cells in different stages of spermatogenesis. The appearance of the c-abl testicular variant was coincident with the entry of the germ cells into their haploid state and suggested that the regulated expression of this proto-oncogene may be important in the normal differentiation of the male germ line.


1997 ◽  
Vol 16 (1) ◽  
pp. 59-72 ◽  
Author(s):  
MEELIS KOLMER ◽  
MARKKU PELTO-HUIKKO ◽  
MARTTI PARVINEN ◽  
CHRISTER HÖÖG ◽  
HANNU ALHO

2004 ◽  
Vol 16 (9) ◽  
pp. 2
Author(s):  
R. J. Aitken

Defective sperm function is the largest defined cause of human infertility, affecting one in twenty Australian males. Despite its prevalence, we are only just beginning to understand the underlying mechanisms. The past decade has seen two major advances in this field: (1) the discovery that Y chromosome deletions play a key role in the aetiology of non-obstructive azoospermia/oligozoospermia; and (2) recognition that oxidative stress can impact upon the functional competence of human spermatozoa through peroxidative damage to the sperm plasma membrane. Oxidative stress has also been found to disrupt the integrity of DNA in the male germ line and may represent an important mechanism by which environmental impacts on human health are mediated. Thus, paternal exposure to various toxicants (cigarette smoke, organic solvents, heavy metals) has been linked with oxidative DNA damage in spermatozoa and developmental defects, including cancer, in the F1 generation. The male germ line becomes particularly vulnerable to such factors during the post meiotic stages of differentiation. Pre-meiotic germ cells always have the option of undergoing apoptosis if DNA damage is severe. However, post meiotic germ cells have lost both the ability to mount an apoptotic response and the capacity for DNA repair. As a result, germ cells are particularly vulnerable to genotoxic agents during spermiogenesis and epididymal maturation. If the fertilizing capacity of the spermatozoa is retained following toxicant exposure, then DNA damage will be transferred to the zygote and must be repaired subsequently by the oocyte and/or early embryo. Aberrant DNA repair at this stage has the potential to create mutations that will compromise embryonic development and, ultimately, the normality of the offspring. Elucidating the causes of oxidative damage in spermatozoa should help resolve the aetiology of conditions such as male infertility, early pregnancy loss and childhood disease, including cancer.


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