Systematic tethering approach assigns function to RNA binding proteins and identifies UBAP2L as an antagonist to FMRP-mediated translation repression (Neuron_polysome_RNA-seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE117292 | GEO | 2023/05/18
REPOSITORIES: GEO
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Project description:Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP11) is a member of the Growth differentiation factors (GDFs), a subfamily of proteins belonging to the transforming growth factor-beta (TGF-β) superfamily (Katoh and Katoh 2006). ). In the past 7-8 years, several high profile studies, showed that systemic restoration of GDF11 levels reverses age-related phenotypes and rejuvenated heart and skeletal muscle in aged mice (Loffredo, Steinhauser et al. 2013, Sinha, Jang et al. 2014), improves insulin sensitivity via restoring pancreatic β-cell function in diabetic mice (Li, Li et al. 2017), and increases proliferation of brain capillary endothelial cells thereby improving the vascular and neurogenic rejuvenation in the brain of aged mice (Katsimpardi, Litterman et al. 2014, Finkenzeller, Stark et al. 2015, Zhang, Guo et al. 2018). Nonetheless, the possible rejuvenation effect of GDF11 was questioned over past years by several other studies. These reports doubted the age-associated decrease of circulating GDF11 level and related phenotypes in the muscle, the heart and the brain (Egerman, Cadena et al. 2015, Rodgers and Eldridge 2015); moreover, restoration of GDF11 levels in old mice had no positive effect on heart structure or function (Smith, Zhang et al. 2015). Increase of GDF11 levels had deleterious effects on aging skeletal muscle regeneration (Egerman, Cadena et al. 2015), suggesting also that supraphysiological levels could lead to cachexia (Hammers, Merscham-Banda et al. 2017). In the field of liver diseases, GDF11 was shown to exhibit tumor suppressive properties in HCC cells (Zhang, Pan et al. 2018, Gerardo-Ramírez, Lazzarini-Lechuga et al. 2019) and to worsen hepatocellular injury and liver regeneration after liver ischemia reperfusion injury (Liu, Dong et al. 2018). From these controverted studies, it is clear that the systemic effects of GDF11 in health and disease are not yet clearly and fully delineated. The aim of the present study was to specifically characterize the role of GDF11 in lipid metabolism and in the progression of the NAFLD disease spectrum, which is currently unknown. We thus aimed at investigating the potential effect of GDF11 on lipid droplet formation in human hepatocytes. Our data strongly suggest that GDF11 supplementation exacerbates, both in presence or absence of FFA, lipid droplet accumulation in two hepatic cell models (HepG2 and Hep3B) by impinging on ALK5/SMAD2/3 dependent signaling pathway.
2019-08-14 | GSE135796 | GEO
Project description:Canonical auxin signalling starts with auxin binding to the receptor complex, followed by modulation of gene transcription and protein abundance (Tan et al., 2007; Chapman and Estelle, 2009; Slade et al., 2017). However, recent studies also showed an alternative mechanism in roots involving intra-cellular auxin perception, but not transcriptional reprogramming (Fendrych et al., 2018). Despite knowledge on effects of auxin on Arabidopsis root growth at the protein and phosphorylation level is increasing (Zhang et al., 2013; Mattei et al., 2013; Slade et al., 2017), it still remains incomplete. To address this gap in our knowledge, we explored the impact of auxin on the root tip proteome and phosphoproteome.
2021-09-09 | PXD021267 | Pride
Project description:FMRP loss-of-function causes Fragile X Syndrome (FXS) and autistic features. FMRP is a polyribosome-associated neuronal RNA-binding protein, suggesting that it plays a key role in regulating neuronal translation, but there has been little consensus regarding either its RNA targets or mechanism of action. Here we use high throughput sequencing of RNAs isolated by crosslinking immunoprecipitation (HITS-CLIP) to identify FMRP interactions with mouse brain polyribosomal mRNAs. FMRP interacts with the coding region of transcripts encoding pre- and postsynaptic proteins, and transcripts implicated in autism spectrum disorders Polyribosomes were prepared from UV254-crosslinked pooled littermate FVB mouse brains as described in detail in published paper PMID 21784246. Polyribosomes were dissociated under denaturing conditions using two different protocols to disrupt ribonucleoprotein complexes. In most experiments Fmr1-null littermates were used in parallel to confirm FMRP specificity. After mild RNAse treatment to reduce the size of RNA to 60-100 nucleotides, endogenous FMRP was immunoprecipitated with one of two antibody combinations, either mixed monoclonal antibodies 7G1-1 and 2F5, or polyclonal antibody ab17722 (Abcam). The ages of the mice were P11, P13, P14, P15, and P25. In addition, to assess a different neuronal polysome-associated protein, as another control, lysates prepared from two samples, the P11 and P13 mice, were split in half and one half IPed with a human anti-Hu antisera as the neuronal Hu proteins are polysome-associated in brain. In sum, 7 FMRP HITS-CLIP experiments were performed including (1) P14 mouse polysomes prepared by Protocol 1 and IPed with 7G1-1/2F5 (2) P14 mouse polysomes prepared by Protocol 1 and IPed with ab17722 (3) P15 mouse polysomes prepared by Protocol 1 and IPed with 7G1-1/2F5 (4) P25 mouse polysomes prepared by Protocol 1 and IPed with 7G1-1/2F5 (5) P25 mouse polysomes prepared by Protocol 1 and IPed with ab17722 (6) P11 mouse polysomes prepared by Protocol 2 and IPed with ab17722 and (7) P13 mouse polysomes prepared by Protocol 2 and IPed with ab17722. FMRP-bound or Hu-bound RNA tags were cloned and submitted for high throughput sequencing on the Life Science 454 platform (samples 1-5) or the Illumina platform (samples 6 and 7 and the 2 Hu samples processed in parallel with samples 6 and 7). Full details are given in PMID 21784246.
2013-03-15 | E-GEOD-45148 | biostudies-arrayexpress
Project description:B. napus, a widely cultivated oilseed crop spanning roughly 35 million hectares world-wide (Faostat , 2022), faces various stress factors including salt stress which reduces plant height, size, and yield (Shahza d et al., 2022; Naheed et al., 2021). Endophytic microorganisms are known to promote plant growth and biomass production (Rho et al., 2018, Azad et al., 2016, Zhang et al., 2019). In this study, inoculation with endophyte Acremonium alternatum increased both fresh and dry weight under salt stress conditions. Further molecular analyses provided insights into potential mechanisms involved, highlighting a putative role of abscisic acid in mediating ROS metabolism and ion sequestering. These findings contribute to our understanding of plant-fungi interactions and offer promising leads for developing novel biological agents to improve crop production under the challenges posed by climate change.
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Project description:Understanding how P4 signaling occurs in endometrial cells is important to guide the development of more effective therapeutic approaches to the numerous reproductive diseases caused by disrupted P4 signaling, resulting in subfertility or infertility (Bunch et al., 2013; Kim et al., 2013; Zhang and Murphy, 2014; Szekeres-Bartho, 2018; Hirota, 2019; Liao et al., 2019). Here, to fill these knowledge gaps, we characterized endometrial PGRMC2 expression throughout the human menstrual cycle and in hEnSCs subjected to an in vitro model of human endometrial decidualization. Additionally, we describe the functional implications of PGRMC2 with a silencing approach assay, integrating RNA-seq and proteomic techniques. We evaluated the functional implication of PGRMC2 in the embryo implantation process with an outgrowth in vitro model. Finally, we also compared endometrial PGRMC2 expression with PGRMC1 and PGR.
2024-06-22 | PXD048494 | Pride
Project description:VSMCs expressing SCA1 have increased proliferative capacity (Dobnikar et al, 2018; Worssam et al, 2022; Pan et al, 2020). We therefore, mapped chromatin accessibility changes using bulk ATAC-seq for SCA1+ and SCA1- lineage traced VSMCs.
2024-04-09 | GSE246646 | GEO
Project description:YTN2 and YTN16 cell lines are subclones established from chemically induced gastric cancer (Yamamoto M et al. Cancer Science 2018). When inoculated to normal C57BL/6 mice, YTN2 spontaneously regresses , while YTN16 grows progressively. To compare expression profiles of these cell lines, we examined microarray analysis.
2020-10-28 | GSE153231 | GEO
Project description:Fragile X syndrome (FXS) is a rare disease but is the most common form of inherited intellectual disability and a leading cause of autism. FXS is due to the absence of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein mainly involved in translational control. Even if this molecular defect is known, no specific therapy is available for FXS. The first alteration observed in the brain of FXS patients and of Fmr1 KO mice, model for FXS, is represented by an abnormal dendritic morphology that is associated with an altered synaptic plasticity. These findings led to numerous studies focused on mature neurons. However, recently, an increasing body of evidence is pointing out the importance of FMRP in the early steps of brain development. Thus, with the purpose to decipher the earliest molecular events leading to FXS we developed a stem-cell-based disease model by knocking-down the expression of Fmr1 in mouse embryonic stem (ES) cells. To gain insights in the pathways that are affected when FMRP is repressed, we performed a gene expression profile analysis comparing total RNA from shFmr1 and shControl ES cells using whole genome mouse microarrays. Transcripts were clustered according to their Gene Ontology classification using the DAVID software. Surprisingly, the most altered functional category was Nervous system development and function, highlighting the role of FMRP also during the earliest steps of neural development. To study the precise role of FMRP in Embryonic stem (ES) cells, we used an RNAi-based loss-of-function strategy by transducing mouse ES cells with a lentivirus expressing GFP and a shRNA targeting the constitutive exon 1 of Fmr1 (shFmr1). A random shRNA (shCT) was used as a control sequence. Transduced cells were sorted by flow cytometry and established as non-clonal cell populations. RNA samples were harvested and profiling experiments were performed in â??dye-balanceâ?? as indicated for each replicate.
2016-07-04 | E-GEOD-71184 | biostudies-arrayexpress
Project description:This submission contains the mass spectrometry files for the manuscript by Nassim Ledoux and Emeline Lelong et al. that describes the mapping FMRP nuclear interactome. AP-MS experiments were performed from U2OS cells and MS files were acquired on Orbitrap Fusion mass spectrometers. Please refer to the individual Table 1 for additional details of submitted files. For questions, please contact Jean-Philippe Lambert (Jean-Philippe.Lambert@crchudequebec.ulaval.ca).
| MSV000092986 | MassIVE
Project description:The fragile X mental retardation protein FMRP is an RNA binding protein that regulates translation of its bound mRNAs through incompletely defined mechanisms. FMRP has been linked to the microRNA pathway and we show here that it is associated with MOV10, a putative helicase that is also associated with the microRNA pathway. We show that FMRP associates with MOV10 in an RNA-dependent manner and facilitates MOV10-association with RNAs in brain. We identified the RNA sequences recognized by MOV10 using iCLIP and found an increased number of G-quadruplexes in the CLIP sites. We provide evidence that MOV10 facilitates microRNA-mediated translation regulation and also has the novel role of increasing the expression of a subset of RNAs by sterically hindering Argonaute2 association. In summary, we have identified a new mechanism for FMRP-mediated translational regulation through its association with MOV10. Comparison of MOV10 siRNA knockdown, irrelevant siRNA control and MOV10 overexpression on total RNA levels
2014-11-20 | E-GEOD-50499 | biostudies-arrayexpress