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1.
Mol Hum Reprod ; 15(3): 165-71, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19168545

RESUMO

The highly conserved Nanos gene was found to encode a translational repressor necessary for germ-cell development in lower organisms. The mammalian homologue, Nanos2, was recently found to be expressed in the mouse germ cells. Since its disruption caused infertility exclusively in males, we sought to study the significance of this gene in human male reproduction. Here, we describe for the first time the expression pattern of the NANOS2 gene in human tissues and show that it is testis specific. We found that NANOS2 protein is present in prenatal germ cells and at later stages in spermatogenesis. To elucidate the role of NANOS2 in human germ-line development, we screened this gene for mutations in 214 males with isolated sterility and spermatogenic abnormalities. We identified two heterozygous variants, each in a different oligospermic patient, the second allele being the wild-type. The influence of the first variant, a missense mutation H68Q on the sterility phenotype, was not obvious since it was accompanied by a microdeletion within the AZF region of the Y chromosome. The second variant contained a silent mutation, H109H. Although both mutations were situated within the most conserved RNA-binding domain and were absent in 400 fertile males, it is not obvious that they cause male infertility.


Assuntos
Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica , Óxido Nítrico Sintase Tipo II/metabolismo , Reprodução/genética , Testículo/metabolismo , Adulto , Sequência de Aminoácidos , Northern Blotting , Western Blotting , Proteínas de Transporte/química , Proteínas de Transporte/genética , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Infertilidade Masculina/genética , Masculino , Dados de Sequência Molecular , Mutação/genética , Óxido Nítrico Sintase Tipo II/química , Óxido Nítrico Sintase Tipo II/genética , Reação em Cadeia da Polimerase , Homologia de Sequência de Aminoácidos
2.
Mol Hum Reprod ; 15(3): 173-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19168546

RESUMO

It has been reported that a highly conserved human protein PUMILIO2 forms a complex with NANOS1 in human male germ cells, as does the Drosophila ancestor Pumilio, which binds Nanos to regulate translation of specific mRNAs. Here, we found that PUMILIO2 interacts also with SNAPIN, a modulator of SNARE complex assembly, which is involved in vesicle trafficking. We demonstrated that SNAPIN interacts additionally with NANOS1 protein. This is the first report demonstrating that the N-terminal region of NANOS1 is necessary for protein binding. In human testis, SNAPIN co-localizes with PUMILIO2 and NANOS1 in prenatal and also in spermatogenic germ cells of the adult. We describe for the first time the expression of SNAPIN in germ cells which raises possibility that SNAPIN plays an extra role in mammals which is germ cell specific. The presence of a coiled-coil domain responsible for protein-protein interaction could enable SNAPIN to be an adaptor of PUMILIO2 and NANOS1, binding other factors to regulate translation in the development of the human germ cells.


Assuntos
Células Germinativas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Humanos , Imuno-Histoquímica , Imunoprecipitação , Técnicas In Vitro , Masculino , Camundongos , Dados de Sequência Molecular , Ligação Proteica , Túbulos Seminíferos/metabolismo , Homologia de Sequência de Aminoácidos , Técnicas do Sistema de Duplo-Híbrido , Proteínas de Transporte Vesicular/química
3.
Mol Reprod Dev ; 74(6): 795-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17154300

RESUMO

The highly conserved Pumilio protein plays crucial roles in fertility of many organisms acting as a repressor of translation, and causing infertility when mutated. Although one of two human Pumilio homologs, PUMILIO2 is expressed mainly in the germ line, its role in mammalian germ cell development has not been reported yet. To shed light on the role of PUMILIO2 in development of the human male germ line, we screened this gene for mutations in 137 patients presenting a variety of phenotypes with spermatogenic failure. The first variant, we identified was a single base substitution within intron 15 (IVS15 + 6G > A). This variant was found in three azoospermic males, the second allele being the wild type. However, this variant was also present among fertile males, as frequently as in the patients. Although location of IVS15 + 6G > A substitution in close proximity to the canonical donor splice site GT, indicates that its influence on splicing cannot be excluded, our preliminary cDNA analysis has not revealed evidence of a splicing abnormality of PUMILIO2 pre-mRNA carrying this variant. Nevertheless, this study provides new interesting variant containing a donor splice site variant, which can be relevant for understanding of splicing mechanism of mammalian genes. The second variant, c.774 C > T transversion (Y258Y) in exon 6 was found only in one patient, but an influence on PUMILIO2 function is not obvious. Altogether, this study shows that variation in the PUMILIO2 gene is very low and it seems improbable that mutations of this gene significantly contribute to male infertility in humans.


Assuntos
Infertilidade Masculina/genética , Polimorfismo Genético , Proteínas de Ligação a RNA/genética , Processamento Alternativo/genética , Substituição de Aminoácidos/fisiologia , Sequência de Bases , Análise Mutacional de DNA , Humanos , Masculino , Mutação , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo
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