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GASZ is essential for male meiosis and suppression of retrotransposon expression in the male germline.

PLoS genetics | Sep 4, 2009

Nuage are amorphous ultrastructural granules in the cytoplasm of male germ cells as divergent as Drosophila, Xenopus, and Homo sapiens. Most nuage are cytoplasmic ribonucleoprotein structures implicated in diverse RNA metabolism including the regulation of PIWI-interacting RNA (piRNA) synthesis by the PIWI family (i.e., MILI, MIWI2, and MIWI). MILI is prominent in embryonic and early post-natal germ cells in nuage also called germinal granules that are often associated with mitochondria and called intermitochondrial cement. We find that GASZ (Germ cell protein with Ankyrin repeats, Sterile alpha motif, and leucine Zipper) co-localizes with MILI in intermitochondrial cement. Knockout of Gasz in mice results in a dramatic downregulation of MILI, and phenocopies the zygotene-pachytene spermatocyte block and male sterility defect observed in MILI null mice. In Gasz null testes, we observe increased hypomethylation and expression of retrotransposons similar to MILI null testes. We also find global shifts in the small RNAome, including down-regulation of repeat-associated, known, and novel piRNAs. These studies provide the first evidence for an essential structural role for GASZ in male fertility and epigenetic and post-transcriptional silencing of retrotransposons by stabilizing MILI in nuage.

Pubmed ID: 19730684 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Animals | Argonaute Proteins | Down-Regulation | Drosophila Proteins | Female | Infertility, Male | Male | Meiosis | Mice | Mice, Inbred C57BL | Mice, Knockout | Proteins | RNA, Small Interfering | Retroelements | Spermatozoa

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Associated grants

  • Agency: NICHD NIH HHS, Id: HD050281
  • Agency: NICHD NIH HHS, Id: T32-HD07165
  • Agency: NICHD NIH HHS, Id: T32 HD007165
  • Agency: NCI NIH HHS, Id: K08-CA134746
  • Agency: NICHD NIH HHS, Id: R01 HD050281
  • Agency: NICHD NIH HHS, Id: U54 HD007495
  • Agency: NICHD NIH HHS, Id: U01-HD060496
  • Agency: NICHD NIH HHS, Id: U54-HD07495
  • Agency: NCI NIH HHS, Id: K08 CA134746

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piRNABank

A web analysis system and resource, which provides comprehensive information on piRNAs in the widely studied mammals. It compiles all the possible clusters of piRNAs and also depicts piRNAs along with the associated genomic elements like genes and repeats on a genome wide map. piRNABank mainly provides data onnamely Human, Mouse, Rat, Zebrafish, Platypus and a fruit fly, Drosophila.Search options have been designed to query and obtain useful data from this online resource. It also facilitates abstraction of sequences and structural features from piRNA data. piRNABank provides the following features: * Simple search * Search piRNA clusters * Search homologous piRNAs * piRNA visualization map * Analysis tools

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