Similar Datasets
Project description:G3BP1 Binds to Guanine Quadruplexes in mRNAs
| PRJNA714642 | ENA
Project description:RNA guanine quadruplexes (rG4) assume important roles in post-transcriptional regulations of gene expression, which are often modulated by rG4-binding proteins. Hence, understanding the biological functions of rG4s requires the identification and functional characterizations of rG4-recognition proteins. By employing a bioinformatic approach based on the analysis of overlap between peaks obtained from rG4-seq analysis and those detected in >230 eCLIP-seq datasets for RNA-binding proteins generated from the ENCODE project, we identified a large number of candidate rG4-binding proteins. We showed that one of these proteins, G3BP1, is able to bind directly to rG4 structures with high affinity and selectivity, where the binding entails its C-terminal RGG domain and is further enhanced by its RRM domain. Additionally, our seCLIP-Seq data revealed that pyridostatin, a small-molecule rG4 ligand, could displace G3BP1 from mRNA in cells, with the most pronounced effects being observed for the 3'-untranslated regions (3'-UTR) of mRNAs. Moreover, luciferase reporter assay results showed that G3BP1 positively regulates mRNA stability through its binding with rG4 structures. Together, we identified a number of candidate rG4-binding proteins and validated that G3BP1 can bind directly with rG4 structures and regulate the stabilities of mRNAs.
| S-EPMC8565330 | biostudies-literature
Project description:Nuclear translocation of the key metabolic enzyme Pyruvate Kinase Isoform 2 (PKM2) is widely observed in cancer, but its contribution to gene regulation and pathogenesis remains unclear. Here we find that PKM2 specifically recognized folded RNA G-quadruplex (rG4) structures in vitro with high affinity. In human cells, nuclear PKM2 bound thousands of precursor mRNAs at potential rG4 sites and translocation of PKM2 to the nucleus resulted in increased expression of rG4-containing mRNAs.
2024-07-31 | GSE179817 | GEO
Project description:RNA binding proteins (RBPs) play a critical role in tumor progression by participating in the post-transcriptional regulation of RNA. However, the expression and function of RBPs in nasopharyngeal carcinoma (NPC) remain elusive. This study identified 5 RBPs (RAN, EZH2, RDM1, HRSP12, and ALYREF) that were up-regulated in NPC and could promote NPC cells migration or proliferation. RAN was first investigated because of its most significant effect on NPC cells. Functionally, RAN facilitated NPC proliferation, migration, and invasion in vitro and in vivo. High expression of RAN was associated with poor prognosis of NPC patients and could be performed as a prognostic biomarker. Mechanistically, RAN mediated the nucleus import of TDP43 and enhanced TDP43 nuclear distribution. On the other hand, RAN was directly bound to the coding sequence of G3BP1 mRNA and served as an adapter to facilitate TDP43 interacting with G3BP1 mRNA 3’untranslated region. Thereby increased G3BP1 mRNA stability in the nucleus and led to up-regulation of G3BP1, which further enhanced ATK/ERK phosphorylation and ultimately promoted NPC proliferation and metastasis.
2024-10-31 | GSE262032 | GEO
Project description:Translational control is a key determinant of protein abundance, which in turns defines the physiology and pathology of human cells. Initiation of translation is highly regulated in eukaryotes and is considered as the rate-limiting step of protein synthesis. mRNA secondary structures in 5’ untranslated region (UTR) and associated helicases have been characterised as key determinants of translation initiation. Nevertheless the transcriptome-wide contribution of non-canonical secondary structures, such as RNA G-quadruplexes (rG4s), to the translation of human mRNAs remains largely unappreciated. Here we use a ribosome profiling strategy to investigate the translational landscape associated to rG4s-containing mRNAs and the contribution of two rG4s-specialised DExH-box helicases, DHX9 and DHX36, to translation initiation in human cells. We show that rG4-forming sequences in 5’-UTR is associated with decreased translation efficiency which correlate with an increased ribosome density within the 5’-UTRs. We found that rG4s contribute to the translation of upstream open reading frames, and as a consequence, thwart the translation of the associated protein coding sequences (CDS). Depletion of the DHX36 and DHX9 helicases demonstrated that the formation of the rG4 structural motif rather than its nucleotide sequence mediate translation initiation. Our findings unveil a role for non-canonical structures in defining alternative 5’ starts for human mRNAs translation initiation.
2018-04-30 | GSE105082 | GEO
Project description:Mitochondrial calcium signaling plays a critical role in mitochondrial homeostasis during non-alcoholic steatohepatitis (NASH) progression. Here, we report Ras‐GTPase activating protein SH3 domain‐binding protein 1 (G3BP1), a core protein of stress granule (SG), significantly upregulated in NAFLD/NASH patients, mouse models and palmitic acid-stimulated hepatocytes. Hepatocyte-specific G3BP1 deficiency attenuates NASH in two dietary mouse models. SG and the mitochondrial import protein TOM70 collaboratively mediate the translocation of G3BP1 to the mitochondria. G3BP1 interacts and stabilizes mitochondrial calcium uptake 1 (MICU1) via inhibiting YME1L1-mediated degradation of MICU1, and also impedes MCU complex activity and assembly, leading to mitochondrial calcium overload. Moreover, metabolic stress suppresses TRIM25-mediated K63-ubiquitination of G3BP1 and subsequent SG disassembly. Pharmacological inhibition of G3BP1 impairs the G3BP1-MICU1 interaction and prevents mitochondrial homeostasis imbalance and NASH progression. Collectively, we uncover the significant role of mitochondrial G3BP1 in mitochondrial homeostasis and NASH progression, which provides a potential target for therapeutic interventions.
2024-08-18 | GSE274650 | GEO
Project description:Rif1 regulates replication timing and repair of double-stranded DNA breaks. Using Chromatin-immunoprecipitation-Sequencing method, we have identified 35 high-affinity Rif1 binding sites in fission yeast chromosomes. Binding sites, preferentially located to the vicinity of dormant origins, tended to contain at least two copies of a conserved motif, CNWWGTGGGGG, and base substitution within these motifs resulted in complete loss of Rif1 binding and activation of late-firing or dormant origins located as far as 50 kb away. We show that Rif1 binding sites adopt G-quadruplex-like structures in vitro in a manner dependent on the conserved sequence as well as on other G-tracts, and that the purified Rif1 preferentially binds to this structure. These results suggest that Rif1 recognizes and binds to G-quadruplex-like structures at selected intergenic regions to generate local chromatin structures that may exert a long-range suppressive effects on origin firing. ChIP-Seq profiles of Rif1 and DNA replicaiton (BrdU-incorporation) vs Input in wildt type, rap1∆, taz1∆, Rif1BS mutants and rif1∆
2015-09-10 | E-GEOD-65293 | biostudies-arrayexpress
Project description:We examine the role of G3bp1, a RNA binding protein and site specific endoribonuclease in gene expression in isolated neonatal cardiomyocytes. RNAseq data from cardiomyocytes were infected with adenoviruses expressing shRNA against G3bp1 (ad-siG3bp1) or Luciferase (ad-siLUC, control) showed significant decrease in transcript abudnnace of cardiac-enriched genes involved in Calcium handling, contraction, action potential and sacromere function. On the other hand increase was observed in genes that regulate Hippo, TNF and TGFb signaling. Knockdown of G3bp1 inhibited endothelin-1 induced cardiomyocyte hypertrophy.
2022-01-14 | GSE184441 | GEO
Project description:RNA binding proteins (RBPs) play a critical role in tumor progression by participating in the post-transcriptional regulation of RNA. However, the expression and function of RBPs in nasopharyngeal carcinoma (NPC) remain elusive. This study identified 5 RBPs (RAN, EZH2, RDM1, HRSP12, and ALYREF) that were up-regulated in NPC and could promote NPC cells migration or proliferation. RAN was first investigated because of its most significant effect on NPC cells. Functionally, RAN facilitated NPC proliferation, migration, and invasion in vitro and in vivo. High expression of RAN was associated with poor prognosis of NPC patients and could be performed as a prognostic biomarker. Mechanistically, RAN mediated the nucleus import of TDP43 and enhanced TDP43 nuclear distribution. On the other hand, RAN was directly bound to the coding sequence of G3BP1 mRNA and served as an adapter to facilitate TDP43 interacting with G3BP1 mRNA 3’untranslated region. Thereby increased G3BP1 mRNA stability in the nucleus and led to up-regulation of G3BP1, which further enhanced ATK/ERK phosphorylation and ultimately promoted NPC proliferation and metastasis.
2024-10-31 | GSE262031 | GEO
Project description:RNA binding proteins (RBPs) play a critical role in tumor progression by participating in the post-transcriptional regulation of RNA. However, the expression and function of RBPs in nasopharyngeal carcinoma (NPC) remain elusive. This study identified 5 RBPs (RAN, EZH2, RDM1, HRSP12, and ALYREF) that were up-regulated in NPC and could promote NPC cells migration or proliferation. RAN was first investigated because of its most significant effect on NPC cells. Functionally, RAN facilitated NPC proliferation, migration, and invasion in vitro and in vivo. High expression of RAN was associated with poor prognosis of NPC patients and could be performed as a prognostic biomarker. Mechanistically, RAN mediated the nucleus import of TDP43 and enhanced TDP43 nuclear distribution. On the other hand, RAN was directly bound to the coding sequence of G3BP1 mRNA and served as an adapter to facilitate TDP43 interacting with G3BP1 mRNA 3’untranslated region. Thereby increased G3BP1 mRNA stability in the nucleus and led to up-regulation of G3BP1, which further enhanced ATK/ERK phosphorylation and ultimately promoted NPC proliferation and metastasis.
2024-10-31 | GSE262034 | GEO