Effects of Trbp deletion on gene expession in mice hearts
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE67658 | GEO | 2015/04/27
SECONDARY ACCESSION(S): PRJNA280580
REPOSITORIES: GEO
Similar Datasets
Project description:We generated the cardiac-specific knockout of Trbp (Trbp-cKO) in mice. We profiled the transcriptome in both wild-type and Trbp-cKO hearts, and found numerous genes were deregulated by deletion of Trbp. We also profiled miRNA expression both wild-type and Trbp-cKO hearts, and found expression of a subset of miRNA species was altered in Trbp-cKO hearts. Examine expression of mRNAs and miRNAs in wild-type and Trbp-cKO hearts
2015-04-27 | E-GEOD-67658 | biostudies-arrayexpress
Project description:TRBP has two known functions as Dicer co-factor and PKR inhibitor. However, the role of TRBP in miRNA biogenesis is controversial and its regulation of PKR in mitosis remains unexplored. Here, we generate TRBP KO HeLa cells and find that TRBP depletion alters Dicer processing sites of a subset of miRNAs, but does not affect Dicer stability, miRNA abundance, or Argonaute loading. By generating PACT, another Dicer interactor, and TRBP/PACT double-KO cells, we further show that TRBP and PACT do not functionally compensate each other and that only TRBP contributes to Dicer processing. We also report that TRBP is hyperphosphorylated by JNK in M phase when PKR is activated by cellular dsRNAs. Hyperphosphorylation potentiates the inhibitory activity of TRBP on PKR, suppressing PKR in M-G1 transition. By generating the first human TRBP KO, our study clarifies the role of TRBP and unveils negative feedback regulation of PKR through TRBP phosphorylation. small RNAs of wild type, TRBP knockout, PACT knockout and TRBP/PACT double knockout cells were sequenced by Illumina Miseq.
2014-09-16 | E-GEOD-61458 | biostudies-arrayexpress
Project description:TRBP has two known functions as Dicer co-factor and PKR inhibitor. However, the role of TRBP in miRNA biogenesis is controversial and its regulation of PKR in mitosis remains unexplored. Here, we generate TRBP KO HeLa cells and find that TRBP depletion alters Dicer processing sites of a subset of miRNAs, but does not affect Dicer stability, miRNA abundance, or Argonaute loading. By generating PACT, another Dicer interactor, and TRBP/PACT double-KO cells, we further show that TRBP and PACT do not functionally compensate each other and that only TRBP contributes to Dicer processing. We also report that TRBP is hyperphosphorylated by JNK in M phase when PKR is activated by cellular dsRNAs. Hyperphosphorylation potentiates the inhibitory activity of TRBP on PKR, suppressing PKR in M-G1 transition. By generating the first human TRBP KO, our study clarifies the role of TRBP and unveils negative feedback regulation of PKR through TRBP phosphorylation.
2014-09-16 | GSE61458 | GEO
Project description:RNA silencing is a post-transcriptional gene-silencing mechanism mediated by microRNAs (miRNAs). However, the regulatory mechanism of RNA silencing during viral infection is unclear. TAR RNA-binding protein (TRBP) is an enhancer of RNA silencing that induces miRNA maturation by interacting with the ribonuclease Dicer. TRBP interacts with a virus sensor protein, laboratory of genetics and physiology 2 (LGP2), in the early stage of viral infection of human cells. Next, it induces apoptosis by inhibiting the maturation of miRNAs, thereby upregulating the expression of apoptosis regulatory genes. In this study, we show that TRBP undergoes a functional conversion in the late stage of viral infection. Viral infection resulted in the activation of caspases that proteolytically processed TRBP into two fragments. The N-terminal fragment did not interact with Dicer but interacted with type I interferon (IFN) signaling modulators, such as protein kinase R (PKR) and LGP2, and induced ER stress. The end results were irreversible apoptosis and suppression of IFN signaling. Our results demonstrate that the processing of TRBP enhances apoptosis, reducing IFN signaling during viral infection.
2024-04-19 | GSE234549 | GEO
Project description:RNA silencing is a post-transcriptional gene-silencing mechanism mediated by microRNAs (miRNAs). However, the regulatory mechanism of RNA silencing during viral infection is unclear. TAR RNA-binding protein (TRBP) is an enhancer of RNA silencing that induces miRNA maturation by interacting with the ribonuclease Dicer. TRBP interacts with a virus sensor protein, laboratory of genetics and physiology 2 (LGP2), in the early stage of viral infection of human cells. Next, it induces apoptosis by inhibiting the maturation of miRNAs, thereby upregulating the expression of apoptosis regulatory genes. In this study, we show that TRBP undergoes a functional conversion in the late stage of viral infection. Viral infection resulted in the activation of caspases that proteolytically processed TRBP into two fragments. The N-terminal fragment did not interact with Dicer but interacted with type I interferon (IFN) signaling modulators, such as protein kinase R (PKR) and LGP2, and induced ER stress. The end results were irreversible apoptosis and suppression of IFN signaling. Our results demonstrate that the processing of TRBP enhances apoptosis, reducing IFN signaling during viral infection.
2024-04-19 | GSE234547 | GEO
Project description:Purpose: Next-generation sequencing (NGS) provides the change of cellular pathways at the transcriptomic level. The overall goal for this research are to compare the transcriptome profiling by NGS in cardiomyocyte-specific FAM210A conditional knockout (cKO) hearts and control (Ctrl) hearts at two different time points and to evaluate the signaling pathways affected by FAM210A deficiency in the heart at the molecular level. Methods: Cardiac mRNA profiles of FAM210A cKO and Ctrl hearts were generated by deep sequencing in triplicate at the late stage (~10 weeks post Fam210a cKO by tamoxifen induction) and in quadruplicates at the early stage (~5 weeks post Fam210a cKO by tamoxifen induction). Results: Using an optimized data analysis workflow from the Genomic Research Center at the University of Rochester, we mapped ~30 millian sequence reads per sample to the mouse genome in the hearts of Ctrl and Fam210a cKO mice at both early and late stages. RNA-seq data comfirmed the knockout of FAM210A in the Fam210a cKO hearts. We identified differentially expressed genes at both early and late stages of FAM210A cKO heart compared with Ctrl hearts (adjust P valuse <0.05). Among upregulated genes, we observed enhanced integrated stress response (ISR) gene signature at both early and late stages in Fam210a cKO hearts compared with Ctrl hearts, including aminoacyl-tRNA synthetases, amino acid synthases, and one-carbon metabolic enzymes. The downregulated genes were not common between the two stages. At the early stage, the top enriched pathways include negative regulation of blood coagulation and wound healing and fatty acid metabolic process. In contrast, at the late stage, the major pathways include sulfide oxidation, glucose import, and mitochondrial ETC complex assembly. Conclusions: Our study provides the first detailed transcriptomic anslysis of cardiomyocyte specific knockout of Fam210a in the heart at two different time-points by NGS. The RNA-seq data reported here provide a framework for comparative investigation of expression profiles in the hearts of FAM210A cKO compared with Ctrl hearts. Based on our analysis, we conclude that ISR is persistently activated in Fam210a cKO hearts, which may be a pro-survival compensatory response caused by the dysfunction of mitochondria in Fam210a cKO hearts. ISR activation can reprogram global cap-dependent translation and cellular metabolism simultaneously.
2023-02-01 | GSE195957 | GEO
Project description:Influenza A virus (IAV), one of the most prevalent respiratory diseases, causes pandemics around the world. The multifunctional non-structural protein 1 (NS1) of IAV is a viral antagonist that suppresses host antiviral response. However, the mechanism by which NS1 modulates the RNA interference (RNAi) pathway remains unclear. Here, we identified interactions between NS1 proteins of Influenza A/PR8/34 (H1N1; IAV-PR8) and Influenza A/WSN/1/33 (H1N1; IAV-WSN) and Dicer’s cofactor TAR-RNA binding protein (TRBP). We found that the N-terminal RNA binding domain (RBD) of NS1 and the first two domains of TRBP protein mediated this interaction. Furthermore, two amino acid residues (Arg at position 38 and Lys at position 41) in NS1 were essential for the interaction. We generated TRBP knockout cells and found that NS1 instead of NS1 mutants (two-point mutations within NS1, R38A/K41A) inhibited the process of microRNA (miRNA) maturation by binding with TRBP. PR8-infected cells showed masking of short hairpin RNA (shRNA)-mediated RNAi, which was not observed after mutant virus-containing NS1 mutation (R38A/K41A, termed PR8/3841) infection. Moreover, abundant viral small interfering RNAs (vsiRNAs) were detected in vitro and in vivo upon PR8/3841 infection. We identify, for the first time, the interaction between NS1 and TRBP that affects host RNAi machinery.
2022-04-15 | GSE189776 | GEO
Project description:we resolved precusor let7 (pre-let-7) and human Dicer-TRBP complex bound precusor let7 (hDicer-TRBP-pre-let-7) secondary structure based on in vivo click selective 2'-hydroxyl acylation and profiling experiment (icSHAPE). We found the free pre-let-7 RNA is more flexible comparing with hDicer-TRBP-pre-7 in the double strand region [10-20nt and 50- 60 nt].
2018-02-14 | GSE110516 | GEO
Project description:MicroRNAs are important regulators of local protein synthesis during neuronal development. We investigated the dynamic regulation of microRNA production and found that the majority of the microRNA-generating complex, consisting of Dicer, TRBP and PACT, specifically associates with intra-cellular membranes in developing neurons. Stimulation with brain-derived neurotrophic factor (BDNF), which promotes dendritogenesis, caused the re-distribution of TRBP from the endoplasmic reticulum into the cytoplasm, and its dissociation from Dicer, in a Ca2+-dependent manner. As a result, the processing of a subset of neuronal precursor microRNAs, among them the dendrite-enriched pre-miR16, was impaired. Decreased production of miR-16-5p, which targeted the BDNF mRNA itself, was rescued by expression of a membrane-targeted TRBP. Moreover, miR-16-5p or membrane-targeted TRBP expression blocked BDNF-induced dendritogenesis, demonstrating the importance of neuronal TRBP dynamics for activity-dependent neuronal development. We propose that neurons employ specialized mechanisms to modulate local gene expression in dendrites, via the dynamic regulation of microRNA biogenesis factors at intracellular membranes of the endoplasmic reticulum, which in turn is crucial for neuronal dendrite complexity and therefore neuronal circuit formation and function.
2017-11-27 | GSE106518 | GEO
Project description:As Grl/Hey2 directly binds DNA through E box motifs and mediates transcription repression, we aim to gain insights into potential target genes of Grl/Hey2 during heart regeneration. We performed RNA-seq analyses using total RNAs collected from 4-HT-treated Tg(cmlc2:creER;cmlc2:nRSGG) hearts and Tg(cmlc2:nRSGG) control hearts, as well as grl5nt-/- mutant hearts and wild-type hearts following ventricular resection at 7 dpa. Using RNA profile analyses, we have identified some potential genes act downstream of Grl/Hey2-dependent transcriptional repression during heart regeneration.
2020-09-14 | GSE129499 | GEO