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Linking Phospho-Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25) to Histone Ubiquitination and Acetylation Essential for Spermatid Development During Spermiogenesis

ABSTRACT: In this study, we examined genome-wide transcriptome profiles of germ cells isolated from GRTH Knock-In and WT mice testis using RNA-Seq. We used homozygous KI mice with R242H mutation in GRTH gene resulting loss of phospho-GRTH to further understand its role in spermatid development during spermiogenesis by analyzing the DEGs from RNA-Seq. The analysis of RNA-Seq data allowed us to find the relevant DEGs related to ubiquitination pathway that are essential for spermatid development. This study using KI mice model demonstrated that loss of phospho-GRTH impairs UBE2J1 and RNF8 dependent histone modifications hampering initial stages of spermatid elongation process.

ORGANISM(S): Mus musculus

PROVIDER: GSE145047 | GEO | 2020/03/04

REPOSITORIES: GEO

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Role of phosphorylated Gonadotropin-Regulated Testicular RNA Helicase (GRTH/DDX25) in the Regulation of Germ Cell Specific mRNAs in Chromatoid Bodies during Spermatogenesis

Project description:In this study, we examined transcriptome profiles of Chromatoid bodies (organelle; CB) of germ cells isolated from GRTH Knock-In (Human GRTH gene with R242H mutation) and WT mice testis using RNA-Seq. We used homozygous GRTH KI mice (which show loss of phospho-GRTH) to further understand the importance of CB and phospho-GRTH and their role in spermatid development during spermiogenesis by analyzing the DEGs from RNA-Seq. The analysis of RNA-Seq data allowed us to find the relevant DEGs related to RNA Transport and Protein processing that are essential for spermatid development. This study using KI mice model demonstrated that loss of phospho-GRTH impairs CB structure and mRNA storage function (in CB) and chromatin compaction hampering initial stages of spermatid elongation process.

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The miRNA expression profiles of round spermatids during GRTH/DDX25 mediated spermiogenesis: mRNA-miRNA Network analysis [miRNAseq]

Project description:GRTH/DDX 25 is a member of the DEAD-box family of RNA helicases that play an essential role in spermatogenesis. Regulation of spermatogenesis occurs at the levels of transcription, post-transcriptional and translational levels which needs to be explored in detail. miRNAs regulate the expression of important genes involved in spermatid elongation process. Differential miRNA expression in round spermatids (RS) of GRTH KO and GRTH-KI mice in comparison with mRNAs remains unexplored. Our miRNAseq analysis of small RNAs obtained from RS reveal differential expression of important miRNAs that regulate spermatid differentiation, apoptosis, chromatin compaction and ubiquitination. mRNAseq analysis of RS isolated from GRTH-KI and GRTH-KO mice models were also carried-out to study the putative miRNA targets and mRNA-miRNA interaction. mRNAseq analysis revealed specific set of mRNAs that are critical for sperm chromatin compaction, ubiquitination and spermatid elongation etc. miRNA-mRNA interaction prediction highlighted differentially expressed/enriched miRNA transcripts whose predicted mRNA targets were differentially expressed. Based on the interaction information of the miRNAs-mRNAs differential analysis, the miRNA-mRNA network was constructed. These results demonstrate the importance of miRNA in the translational arrest and stability of germ cell specific mRNAs which are critical for later stages of spermiogenesis and fertility.

2023-03-20 | GSE222627 | GEO

The miRNA expression profiles of round spermatids during GRTH/DDX25 mediated spermiogenesis: mRNA-miRNA Network analysis [mRNAseq]

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Linking Phospho-Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25) to Histone Ubiquitination and Acetylation Essential for Spermatid Development During Spermiogenesis

Project description:Linking Phospho-Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25) to Histone Ubiquitination and Acetylation Essential for Spermatid Development During Spermiogenesis

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Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is essential for spermatid development and completion of spermatogenesis.

Project description: Not available

| S-EPMC404052 | biostudies-literature

Linking Phospho-Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25) to Histone Ubiquitination and Acetylation Essential for Spermatid Development During Spermiogenesis.

Project description: Not available

| S-EPMC7242631 | biostudies-literature

Differential miroRNA expression in round spermatids of GRTH null mice compared to wild type.

Project description:miRNA expression profiles for round spermatids of wild type and GRTH knock-out mice were determined by Rodent TaqMan® Low Density miRNA Arrays A v2.0 (TLDA, Applied Biosystem). Purified round spermatids were prepared from the testis of wild type and GRTH null mice (C57BL/6 strain). Equal amount of total RNA from 20 mice (wild type or GRTH KO) was pooled prior to gene expression analysis.

2012-01-31 | E-GEOD-33969 | biostudies-arrayexpress

Differential miroRNA expression in round spermatids of GRTH null mice compared to wild type.

2012-01-31 | GSE33969 | GEO

Role of gonadotropin regulated testicular RNA helicase (GRTH/Ddx25) on polysomal associated mRNAs in mouse testis.

Project description: Not available

| S-EPMC3316541 | biostudies-literature

Tsga8 is required for spermatid morphogenesis and male fertility in mice

Project description:During spermatogenesis, intricate gene expression is coordinately regulated by epigenetic modifiers, which are required for differentiation of spermatogonial stem cells (SSCs) contained among undifferentiated spermatogonia. We previously found that KMT2B conveys H3K4me3 at bivalent and monovalent promoters in undifferentiated spermatogonia. Because these genes are expressed late in spermatogenesis or during embryogenesis, we expect that many of them are potentially programmed by KMT2B for future expression. Here, we show that one of the genes targeted by KMT2B, Tsga8, plays an essential role in spermatid morphogenesis. Loss of Tsga8 in mice leads to male infertility associated with abnormal chromosomal distribution in round spermatids, malformation of elongating spermatid heads and spermiation failure. Tsga8 depletion leads to dysregulation of thousands of genes, including the X chromosome genes that are reactivated in spermatids, and insufficient nuclear condensation accompanied by reductions of TNP1 and PRM1, key factors for histone-to-protamine transition. Intracytoplasmic sperm injection (ICSI) of spermatids rescued the infertility phenotype, suggesting competency of the spermatid genome for fertilization. Thus, Tsga8 is a KMT2B target that is vitally necessary for spermiogenesis and fertility.

2021-04-16 | GSE147805 | GEO

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