Male specific conserved LncRNA TSCL1 regulated target mRNA translation by interaction with PIWIL1 [lncRNA-seq]
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ABSTRACT:
PROVIDER: PRJNA1197448 | ENA |
REPOSITORIES: ENA
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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
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 | GSE284143 | GEO
Project description:Male specific conserved LncRNA TSCL1 regulated target mRNA translation by interaction with PIWIL1 [Ribo-seq]
| PRJNA1197449 | ENA
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
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
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) . Examine mRNA profile in two groups of primary cultured neurons with electroporation of control or RNAi plasmid.
2016-06-22 | E-GEOD-48236 | biostudies-arrayexpress
Project description:A fundamental goal of genomics is to identify the complete set of expressed proteins. Automated annotation strategies rely on assumptions about protein-coding sequences (CDSs), e.g., they are conserved, do not overlap, and exceed a minimum length. However, an increasing number of newly discovered proteins violate these rules. Here we present an experimental and analytical framework, based on ribosome profiling and linear regression, for systematic identification and quantification of translation. Application of this approach to lipopolysaccharide-stimulated mouse dendritic cells and HCMV-infected human fibroblasts identifies thousands of novel CDSs, including micropeptides and variants of known proteins, that bear the hallmarks of canonical translation and exhibit comparable translation levels and dynamics to annotated CDSs. Remarkably, many translation events are identified in both mouse and human cells even when the peptide sequence is not conserved. Our work thus reveals an unexpected complexity to mammalian translation suited to provide both conserved regulatory or protein-based functions. 37 ribosome footprint samples from mouse BMDCs across a time course of LPS stimulation and in the presence or absence of translation inhibitors cycloheximide, harringtonine, or lactimidomycin. A mock (non-LPS stimulated) time course is also included, collected in the presence of cycloheximide. Two replicates are available for the LPS timecourse under CHX treatment.
2015-12-03 | E-GEOD-74139 | biostudies-arrayexpress
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
Project description:EPR is a long non-coding RNA (lncRNA) that controls cell proliferation in mammary gland cells by regulating gene transcription. Here, we report on Mettl7a1 as a direct target of EPR. We show that EPR induces Mettl7a1 transcription by rewiring three-dimensional chromatin interactions at the Mettl7a1 locus. Our data indicate that METTL7A1 contributes to EPR-dependent inhibition of TGF-β signaling. METTL7A1 is absent in tumorigenic murine mammary gland cells and its human ortholog (METTL7A) is downregulated in breast cancers. Importantly, re-expression of METTL7A1 in 4T1 tumorigenic cells attenuates their transformation potential, with the putative methyltransferase activity of METTL7A1 being dispensable for its biological functions. We found that METTL7A1 localizes in the cytoplasm whereby it interacts with factors implicated in the early steps of mRNA translation, associates with ribosomes, and affects the levels of target proteins without altering mRNA abundance. Overall, our data indicates that METTL7A1 —a transcriptional target of EPR— modulates translation of select transcripts.
2022-08-12 | PXD034398 | Pride
Project description:A fundamental goal of genomics is to identify the complete set of expressed proteins. Automated annotation strategies rely on assumptions about protein-coding sequences (CDSs), e.g., they are conserved, do not overlap, and exceed a minimum length. However, an increasing number of newly discovered proteins violate these rules. Here we present an experimental and analytical framework, based on ribosome profiling and linear regression, for systematic identification and quantification of translation. Application of this approach to lipopolysaccharide-stimulated mouse dendritic cells and HCMV-infected human fibroblasts identifies thousands of novel CDSs, including micropeptides and variants of known proteins, that bear the hallmarks of canonical translation and exhibit comparable translation levels and dynamics to annotated CDSs. Remarkably, many translation events are identified in both mouse and human cells even when the peptide sequence is not conserved. Our work thus reveals an unexpected complexity to mammalian translation suited to provide both conserved regulatory or protein-based functions.
2015-12-03 | GSE74139 | GEO