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nanos C2HC-type zinc finger 1 OKDB#: 1370
 Symbols: NANOS1 Species: human
 Synonyms: NOS1, NOS-1, SPGF12, EC_Rep1a, ZC2HC12A  Locus: 10q26.11 in Homo sapiens


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General Comment Nanos encodes a product involved in female meiosis chromosome segregation which is expressed in the adult (cystoblast , female germline stem cell and germline cyst ) and embryo (pole cell ). It has been sequenced and its amino acid sequence contains a zn-finger CCHC type .

NCBI Summary: This gene encodes a CCHC-type zinc finger protein that is a member of the nanos family. This protein co-localizes with the RNA-binding protein pumilio RNA-binding family member 2 and may be involved in regulating translation as a post-transcriptional repressor. Mutations in this gene are associated with spermatogenic impairment. [provided by RefSeq, Sep 2015]
General function RNA binding
Comment
Cellular localization Cytoplasmic
Comment
Ovarian function Germ cell development, Oogenesis
Comment Marion K?nner, et al reported that a zebrafish nanos-related gene is essential for the development of primordial germ cells. Asymmetrically distributed cytoplasmic determinants collectively termed germ plasm have been shown to play an essential role in the development of primordial germ cells (PGCs). Marion K?nner, et al report the identification of a nanos-like (nanos1) gene, which is expressed in the germ plasm and in the PGCs of the zebrafish. Several mechanisms act in concert to restrict the activity of Nanos1 to the germ cells including RNA localization and control over the stability and translatability of the RNA. Reducing the level of Nanos1 in zebrafish embryos revealed an essential role for the protein in ensuring proper migration and survival of PGCs in this vertebrate model organism. Verrotti AC, et al 2000 reported that Nanos interacts with cup in the female germline of Drosophila. Nanos (Nos) is a translational regulator that governs abdominal segmentation of the Drosophila embryo in collaboration with Pumilio (Pum). In the embryo, the mode of Nos and Pum action is clear: they form a ternary complex with critical sequences in the 3'UTR of hunchback mRNA to regulate its translation. Nos also regulates germ cell development and survival in the ovary. While this aspect of its biological activity appears to be evolutionarily conserved, the mode of Nos action in this process is not yet well understood. In this report, the authors show that Nos interacts with Cup, which is required for normal development of the ovarian germline cells. nos and cup also interact genetically--reducing the level of cup activity specifically suppresses the oogenesis defects associated with the nos(RC) allele. This allele encodes a very low level of mRNA and protein that, evidently, is just below the threshold for normal ovarian Nos function. Taken together, these findings are consistent with the idea that Nos and Cup interact to promote normal development of the ovarian germline. They further suggest that Nos and Pum are likely to collaborate during oogenesis, as they do during embryogenesis. nanos1 is required to maintain oocyte production in adult zebrafish. Draper BW et al. Development of the germline requires the specification and survival of primordial germ cells (PGCs) in the embryo as well as the maintenance of gamete production during the reproductive life of the adult. These processes appear to be fundamental to all Metazoans, and some components of the genetic pathway regulating germ cell development and function are evolutionarily conserved. In both vertebrates and invertebrates, nanos-related genes, which encode RNA-binding zinc finger proteins, have been shown to play essential and conserved roles during germ cell formation. In Drosophila, maternally supplied nanos is required for survival of PGCs in the embryo, while in adults, nanos is required for the continued production of oocytes by maintaining germline stem cells self-renewal. In mice and zebrafish, nanos orthologs are required for PGC survival during embryogenesis, but a role in adults has not been explored. We show here that nanos1 in zebrafish is expressed in early stage oocytes in the adult female germline. We have identified a mutation in nanos1 using a reverse genetics method and show that young female nanos mutants contain oocytes, but fail to maintain oocyte production. This progressive loss of fertility in homozygous females is not a phenotype that has been described previously in the zebrafish and underlines the value of a reverse genetics approach in this model system.
Expression regulated by
Comment
Ovarian localization Primordial Germ Cell, Oocyte
Comment Expression decreases in mouse oocyte based on DNA microarray data.////////Nanos maintains germline stem cell self-renewal by preventing differentiation. Wang Z, et al . Despite much progress in understanding how extrinsic signaling regulates stem cell self-renewal, little is known about how cell-autonomous gene regulation controls this process. In Drosophila ovaries, germline stem cells (GSCs) divide asymmetrically to produce daughter GSCs and cystoblasts, the latter of which develop into germline cysts. Here, we show that removing the translational repressor Nanos from either GSCs or their precursors, the primordial germ cells (PGCs), causes both cell types to differentiate into germline cysts. Thus, Nanos is essential for both establishing and maintaining GSCs by preventing their precocious entry into oogenesis. These functions are likely achieved by repressing the translation of differentiation factors in PGCs and GSCs.
Follicle stages
Comment
Phenotypes
Mutations 1 mutations

Species: human
Mutation name:
type: naturally occurring
fertility: None
Comment: Mutations of NANOS1, a human homologue of the Drosophila morphogen, are associated with a lack of germ cells in testes or severe oligo-astheno-teratozoospermia. Kusz-Zamelczyk K et al. (2013) The Nanos gene is a key translational regulator of specific mRNAs involved in Drosophila germ cell development. Disruption of mammalian homologues, Nanos2 or Nanos3, causes male infertility in mice. In humans, however, no evidence of NANOS2 or NANOS3 mutations causing male infertility has been reported. Although Nanos1 seems dispensable for mouse reproduction, we sought to analyse for the first time its homologue in infertile men. A group of 195 patients manifesting non-obstructive azoospermia or oligozoospermia were tested for mutations of the NANOS1 gene, using single-strand conformation polymorphism and DNA sequencing. Three types of NANOS1 gene mutations were identified in five patients and were absent in 800 chromosomes of fertile men. Pedigree analysis indicated a dominant inheritance pattern with penetration limited to males. Two mutations caused deletions of single amino acids, p.Pro77_Ser78delinsPro and p.Ala173del, each of them identified in two unrelated patients. Both types of deletions were located in the NANOS1 N-terminus (responsible for protein interactions) and were associated with a lack of germ cells in testes. Interestingly, the Pro77_Ser78delinsPro mutation altered interaction of NANOS1 with a microRNA biogenesis factor, GEMIN3. The third identified mutation, p.[(Arg246His; Arg276Tyr)], found in the C-terminal RNA-binding domain, was present in a single oligo-astheno-teratozoospermic man. We bioinformatically demonstrated that the p.Arg246His substitution causes a decrease in the positive charge of this domain, potentially altering RNA-binding. This is the first report describing the association of NANOS1 gene mutations with human infertility. Two different infertility phenotypes may reflect distinct functions of N-terminal versus C-terminal regions of NANOS1.//////////////////

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created: Nov. 22, 2001, 4:45 a.m. by: hsueh   email:
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last update: Feb. 14, 2021, 6:22 p.m. by: hsueh    email:



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