Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Male specific conserved LncRNA TSCL1 regulated target mRNA translation by interaction with PIWIL1 [Ribo-seq]

ABSTRACT: Long non-coding RNAs are known to play crucial roles in various physiological processes in mammals, yet their functions in spermatogenesis remain largely underexplored. Here, we have identified a distinct category of conserved haploid spermatids-associated long non-coding RNAs (cHS-LncRNAs) characterized by their sequence-based conservation, specific expression in the testis, and elevated expression levels in haploid spermatids. Among these, we found that the testis specific conserved LncRNA 1 (Tscl1) exhibits the highest expression in round spermatids. Deletion of Tscl1 in mice exhibits reduced sperm motility, disordered mitochondrial sheath structure, abnormal fatty acid metabolism, and results in male infertility. Mechanistically, Tscl1 directly interacts with PIWIL1 and HuR via its 5′ end stem-loop structure and multiple AU-rich elements, respectively. This binding pattern promotes the formation of the PIWIL1/eIF3f/HuR/eIF4G3 supercomplex, regulating the translation efficiency of fatty acid metabolism-associated mRNAs within the chromatoid body. Furthermore, the region where TSCL1 interacts with PIWIL1 is significantly enriched with TSCL1 variants identified in patients with non-obstructive azoospermia (NOA) compared to those in the fertile controls (OR=5.992, P=0.020, NCase=1,338, NControl=2,664). Taken together, our findings elucidate the critical role of Tscl1 in regulating the translation efficiency of target mRNAs through its collaboration with PIWIL1 and HuR during spermiogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE284143 | GEO | 2024/12/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Male specific conserved LncRNA TSCL1 regulated target mRNA translation by interaction with PIWIL1 [lncRNA-seq]

Project description:Long non-coding RNAs are known to play crucial roles in various physiological processes in mammals, yet their functions in spermatogenesis remain largely underexplored. Here, we have identified a distinct category of conserved haploid spermatids-associated long non-coding RNAs (cHS-LncRNAs) characterized by their sequence-based conservation, specific expression in the testis, and elevated expression levels in haploid spermatids. Among these, we found that the testis specific conserved LncRNA 1 (Tscl1) exhibits the highest expression in round spermatids. Deletion of Tscl1 in mice exhibits reduced sperm motility, disordered mitochondrial sheath structure, abnormal fatty acid metabolism, and results in male infertility. Mechanistically, Tscl1 directly interacts with PIWIL1 and HuR via its 5′ end stem-loop structure and multiple AU-rich elements, respectively. This binding pattern promotes the formation of the PIWIL1/eIF3f/HuR/eIF4G3 supercomplex, regulating the translation efficiency of fatty acid metabolism-associated mRNAs within the chromatoid body. Furthermore, the region where TSCL1 interacts with PIWIL1 is significantly enriched with TSCL1 variants identified in patients with non-obstructive azoospermia (NOA) compared to those in the fertile controls (OR=5.992, P=0.020, NCase=1,338, NControl=2,664). Taken together, our findings elucidate the critical role of Tscl1 in regulating the translation efficiency of target mRNAs through its collaboration with PIWIL1 and HuR during spermiogenesis.

2024-12-17 | GSE284142 | GEO

Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression

Project description:Piwi proteins are a subfamily of Argonaute proteins that maintain germ cells in eukaryotes. However, the role of their human homologues in cancer stem cells and more broadly in cancer is poorly understood. Here, we report that the Piwi-like family members, including Piwil1 (Hiwi), are overexpressed in glioblastoma (GBM), with Piwil1 levels most frequently elevated. Piwil1 is enriched in glioma stem cells (GSCs) and helps to maintain their self-renewal. GSCs were transduces with control non-targeting shRNAs (shNT) and shPiwil1 (#1 and #2) and global gene expression was analyzed to identify Piwil1 downscream singalings.

2020-10-30 | GSE160437 | GEO

piRNA-independent Function of PIWIL1 as a Novel co-activator for Anaphase Promoting Complex/Cyclosome (APC/C) to Drive Pancreatic Cancer Metastasis

Project description:Piwi proteins are normally restricted in germ cells to suppress transposons through association with piRNAs, but are also frequently activated in many types of human cancers. Of great puzzle is the lack of induction of corresponding piRNAs in cancer cells, as we document here in human pancreatic ductal adenocarcinomas (PDAC), implying that such germline-specific proteins are somehow hijacked to promote tumorigenesis through different mode of action. To pursue the underlying mechanism, we now demonstrate that in the absence of piRNAs, the aberrantly induced human PIWIL1 in PDAC functions as an oncoprotein by activating the Anaphase Promoting Complex/Cyclosome (APC/C), which then targets a critical cell adhesion-related protein Pinin to enhance PDAC metastasis. This is in contrast to piRNA-dependent PIWIL1 ubiquitination and removal by APC/C during late spermiogenesis. These findings thus unveil an piRNA-dependent mechanism to switch PIWIL1 from a substrate in spermatids to a co-activator of APC/C in human cancer cells.

2020-02-01 | GSE141340 | GEO

The NMD endonuclease SMG6 co-operates with the piRNA pathway in germ granules to shape the male germ cell transcriptome

Project description:Nonsense-mediated RNA decay (NMD) is a conserved RNA turnover pathway. Here we report that the sole endonuclease in the NMD pathway, SMG6, is essential for the male germline. Germ-cell conditional knockout (cKO) of Smg6 causes complete arrest of spermatogenesis at the early haploid cell stage. Smg6-cKO round spermatids accumulate NMD target mRNAs with long 3’ untranslated regions (UTRs) and fail to eliminate transcripts normally expressed during meiosis, the previous step in spermatogenesis. SMG6 and PIWI-interacting (pi) RNA pathway components are highly enriched in the chromatoid body (CB), a specialized cytoplasmic granule in male germ cells. This led to the intriguing possibility that the CB is a site where SMG6 and the piRNA pathway co-operate to regulate RNA metabolism. Several findings supported this hypothesis: (i) SMG6 and the piRNA-binding protein PIWIL1 have almost identical temporal expression and localization patterns, (ii) SMG6 and PIWIL1 physically interact, (iii) scores of genes upregulated in Smg6-cKO round spermatids overlap with those upregulated in Piwil1-KO round spermatids, and (iv) the phenotypic defects caused by SMG6 loss phenocopies the defects caused by PIWIL1 loss. Together, our results demonstrate that SMG6 is an essential regulator of the male germline transcriptome and highlight the CB as a molecular platform coordinating RNA regulatory pathways to control sperm production and fertility.

2022-09-27 | GSE182518 | GEO

Genome-wide analysis of rats' mRNA profile after knocking down PIWIL1 in embryonic cultured neurons.

Project description:We have demonstrated that PIWIL1 can regulate neuronal radial migration during corticogenesis. In order to explore the mechanism, we carried out high-throughtput sequencing (mRNA profile) to define downstream target of PIWIL during the process of neuronal migration. And we found the expression level of several microtubule-associated proteins decreased after downregulation of PIWIL1. Therefore, PIWIL1 plays an important role in neuronal migration by regulating the expression microtubule-associated proteins (such as Map1B, Map2, Tau) .

2016-06-22 | GSE48236 | GEO

Genome-wide analysis of rats' mRNA profile after knocking down PIWIL1 in embryonic cultured neurons.

2016-06-22 | E-GEOD-48236 | biostudies-arrayexpress

Bulk RNA-Seq of whole testis sampled from juvenile mice

Project description:Spermatogenesis is a recurring differentiation process that results in the production of male gametes within the testes. During this process, spermatogonial stem cells differentiate to form spermatocytes, which undergo two rounds of meiotic division to form haploid spermatids. Throughout spermiogenesis, round spermatids elongate to form mature sperm. To profile maturing cell types, we generated bulk RNA-seq data from whole testis undergoing the first round of spermatogenesis between post-natal day P6 and P35. We also compared these libraries to adult samples.

2018-10-09 | E-MTAB-6934 | biostudies-arrayexpress

RNA-Immunoprecipitation of PIWIL1/piRNA complexes in COLO 205 cells and deep-sequencing of associated small RNAs with NGS technologies

Project description:To evaluate PIWIL1/piRNAs association in the metastatic COLO 205 cell line, we performed an RNA-immunoprecipitation experiment followed by small RNA deep-sequencing (RIP-Seq). For the identification of PIWIL1/piRNA complexes, independent reactions were carried out with two different antibodies (IP1 and IP2); non-specific interactions were computationally filtered out using a No Antibody control (No Ab).

2020-08-05 | E-MTAB-8121 | biostudies-arrayexpress

Analysis of Global Protein Expression in PIWIL1 knockdown PDAC cell line

Project description:In contrast to the great advances in understanding of the functions of Piwi in germlines, their actions in cancer cells remain less clear. In particular, Piwi proteins have been asserted as oncoproteins, but little is known about how their oncogenic function is achieved in cancer cells. We conducted mass spectrometry-based quantitative proteomic analyses to monitor the proteome changes upon PIWIL1 downregulation in PDAC cell line.

2020-02-18 | PXD017452 | Pride

Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression

Project description:Piwil1 Regulates Glioma Stem Cell Maintenance and Glioblastoma Progression

| PRJNA673195 | ENA