Similar Datasets
Project description:TRIM25 E3 ubiquitin ligase is a new RNA-binding protein. We present the first high-throughput analysis of the molecular interactomes of TRIM25. We show that TRIM25 is a bona fide RNA-binding protein that interacts with numerous coding and non-coding transcripts. This suggests that TRIM25 could play a role in the regulation of RNA metabolism.
2018-07-27 | GSE104949 | GEO
Project description:Ubiquitination plays an important role in proliferating and invasive characteristic of glioblastoma (GBM), similar to many other cancers. Tripartite motif 25 (TRIM25) is a member of the TRIM family of proteins, which are involved in tumorigenesis through substrate ubiquitination. Here, we found TRIM25 is upregulated in GBM and promotes glioblastoma cell growth and invasion, both in vitro and in vivo. Subsequently, we screened a panel of proteins that interact with TRIM25; mass spectrometry and co-immunoprecipitation showed that NONO was a potential substrate of TRIM25. TRIM25 knockdown reduced the K63-linked ubiquitination of NONO, which suppressed the splicing function of NONO. The dysfunctional NONO further leads to the retention of the second intron in the pre-mRNA of PRMT1 and inhibit the activation of the PRMT1/c-MYC pathway. In summary, we demonstrated that TRIM25 promotes glioblastoma cell growth and invasion by regulating the PRMT1/c-MYC pathway through mediation of the splicing factor NONO. Efforts to target the E3 ligase activity of TRIM25 or the complex interactions between TRIM25 and NONO may be useful in the treatment of GBM.
2023-07-11 | GSE236661 | GEO
Project description:We report high-throughput profiling of TRIM25 binding sites in triple negative breast cancer cells.
2017-04-01 | GSE79588 | GEO
Project description:To analyze the effect of TRIM25 on gene expression, TRIM25 was knocked out in MCF7 cells. To understand a possible contribution of p300 on this gene regulation, p300 was inhibited. RNA seq was performed to see changes in the whole transcriptome
2022-10-11 | GSE215084 | GEO
Project description:Circular RNAs (circRNAs) are a class of covalently closed single-stranded RNAs that have been demonstrated to involve in cancer progression. Here, we identify circNDUFB2 is downregulated in non-small cell lung cancer (NSCLC) tissues, and it negatively correlates with the malignant features. Elevated circNDUFB2 inhibits growth and metastasis of NSCLC cells. circNDUFB2 functions as a scaffold to enhance interaction of TRIM25 with IGF2BPs by forming a TRIM25/circNDUFB2/IGF2BPs ternary complex. The resultant ternary complex facilitates ubiquitination degradation of IGF2BPs, and N6-methyladenosine (m6A) modification of circNDUFB2 increases ubiquitination efficiency of TRIM25 for IGF2BPs. Moreover, circNDUFB2 can be recognized by RIG-I, then activates RIG-I-MAVS signaling cascades and recruits immune cells into tumor microenvironment (TME). Our data provide evidences that circNDUFB2 participates in degradation of IGF2BPs and activation of anti-tumor immunity in NSCLC progression. These findings reveal a dual-role pattern of circNDUFB2 action involved in protein ubiquitination degradation and cellular immune response.
2020-10-14 | GSE158695 | GEO
Project description:TRIM25 ChIP-seq on human K562 For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2017-01-04 | GSE91581 | GEO
Project description:TRIM25 ChIP-seq on human K562 For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2019-03-03 | GSE127419 | GEO
Project description:The tripartite motif (TRIM) family of E3 ubiquitin ligases is well known for its roles in antiviral restriction and innate immunity regulation, in addition to many other cellular pathways. In particular, TRIM25-mediated ubiquitination affects both carcinogenesis and antiviral response. While individual substrates have been identified for TRIM25, it remains unclear how it regulates diverse processes. Here we characterized a mutation, R54P, critical for TRIM25 catalytic activity, which we successfully utilized to “trap” substrates. We demonstrated that TRIM25 targets proteins implicated in stress granule formation (G3BP1/2), nonsense-mediated mRNA decay (UPF1), and nucleoside synthesis (NME1). R54P abolishes TRIM25 inhibition of alphaviruses independently of the host interferon response, suggesting that this antiviral effect is a direct consequence of ubiquitination. Consistent with that, we observed diminished antiviral activity upon knockdown of several TRIM25-R54P specific interactors including NME1. Our findings highlight that multiple substrates mediate the cellular and antiviral activities of TRIM25, illustrating the multi-faceted role of this ubiquitination network in diverse biological processes.
2022-08-02 | PXD034024 | Pride
Project description:The RNA-binding protein PARP13 is a primary factor in the innate antiviral response. PARP13 can suppress translation and drive decay of bound viral and host RNA. PARP13 interacts with many proteins encoded by interferon-stimulated genes (ISG) to perform its antiviral activities, such as activation of the pathway mediated by post-translational addition ISG15 or ISGylation. The RNA-binding domains of both PARP13 and its primary cofactor, TRIM25, are required for antiviral activity. Here we perform enhanced crosslinking immunoprecipitation (eCLIP) and RNA-seq to investigate the role of PARP13 expression and RNA binding in transcriptome regulation within human cells. We find that PARP13 regulates the transcriptome in basal and antiviral states and that the antiviral response shifts PARP13 target localization, but not its binding preferences. We demonstrate that PARP13 expression supports the expression of ISGylation-related genes, including TRIM25. Using the common targets PARP13 and TRIM25 share, we assess their spatial relationship along transcripts and show that PARP13 and TRIM25 associate in part via RNA-protein interactions. Evidence from genomic data and molecular biology experiments provide insight into the geometry of PARP13's interface with its cofactor TRIM25 and implicates PARP13 in creating and maintaining a cellular environment poised for an antiviral response.
2023-09-11 | GSE215250 | GEO
Project description:Therapy resistance is still a major reason for treatment failure in colorectal cancer (CRC). Previously, we identified the E3 ubiquitin ligase TRIM25 as a novel suppressor of caspase-2 translation, thereby contributing to apoptosis resistance of CRC cells towards chemotherapeutic drugs. We herein report the executioner caspase-7 being a further target of TRIM25. Results from gain and loss-of-function approaches and actinomycin D experiments indicate that TRIM25 attenuates caspase-7 expression mainly through a decrease in mRNA stability. Data from RNA pull-down assays with immunoprecipitated TRIM25 truncations indicate a direct TRIM25 binding to caspase-7 mRNA which is mediated by the PRY/SPRY domain which is also known to be highly relevant for protein-protein interactions. By employing TRIM25 immunoprecipitation, we identified the heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) as a novel TRIM25 binding protein involved in the control of caspase-7 mRNA stability. Notably, the interaction of both proteins was highly sensitive to RNase A treatment and again depended on the PRY/SPRY domain, thus indicating an indirect interaction of both proteins which is achieved through a common RNA binding. Ubiquitin affinity chromatography showed that hnRNPH1 and TRIM25 are targets of ubiquitin modification. Functionally, the ectopic expression of caspase-7 in CRC cells caused an increase in poly ADP-ribose polymerase (PARP) cleavage concomitant with a significant increase in apoptosis. Collectively, the negative regulation of caspase-7 by TRIM25 via hnRNPH1 implies a novel survival mechanism underlying chemotherapeutic drug resistance of CRC cells. Targeting of TRIM25 could therefore offer a promising strategy for reducing therapy resistance in CRC patients.
2023-01-05 | PXD037182 | Pride