TRA2B

更新于：2025-05-07

基本信息

别名

Htra2-beta、PPP1R156、SFRS10

+ [7]

简介

Sequence-specific RNA-binding protein which participates in the control of pre-mRNA splicing. Can either activate or suppress exon inclusion. Acts additively with RBMX to promote exon 7 inclusion of the survival motor neuron SMN2. Activates the splicing of MAPT/Tau exon 10. Alters pre-mRNA splicing patterns by antagonizing the effects of splicing regulators, like RBMX. Binds to the AG-rich SE2 domain in the SMN exon 7 RNA. Binds to pre-mRNA.

关联

项与 TRA2B 相关的药物

ASO-1570

靶点

TRA2B

作用机制

TRA2B inhibitors

在研机构

The Jackson Laboratory [+1]

原研机构

University of Connecticut Health Center [+1]

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TRA2B 相关的临床结果

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100 项与 TRA2B 相关的转化医学

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0 项与 TRA2B 相关的专利（医药）

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103

项与 TRA2B 相关的文献（医药）

2025-01-07·Biochemistry

Zinc and RNA Binding Is Linked to the Conformational Flexibility of ZRANB2: A CCCC-Type Zinc Finger Protein

Article

作者: Deredge, Daniel J. ; Kihn, Kyle C. ; Michel, Sarah L. J. ; Reitz, Abigail D. ; Hursey, Matthew S.

Ran-binding domain-containing protein 2 (ZRANB2) is a zinc finger (ZF) protein that plays a key role in alternative splicing. ZRANB2 is composed of two ZF domains that contain four invariant cysteine residues per domain. ZRANB2 binds RNA targets that contain AGGUAA sequence motifs. Three constructs of ZRANB2, ZRANB2-ZF1 (first ZF domain), ZRANB2-ZF2 (second ZF domain), and ZRANB2-2D (both ZF domains), were isolated in the apo form and shown to bind Zn(II) via UV-visible-monitored competitive titrations with Co(II) as a spectroscopic probe. Zn binding to each construct led to the adoption of a limited secondary structure of each domain, as measured by circular dichroism (CD). Hydrogen-deuterium exchange coupled with mass spectrometry (HDX-MS) of the two-domain construct, ZRANB2-2D, revealed that both ZF domains adopt a more rigid structure upon Zn binding. Zn binding to the first ZF domain resulted in a greater decrease in the conformational dynamics than Zn binding to the second ZF domain. RNA binding to TRA2B pre-mRNA, a physiological splicing target, was measured by fluorescence anisotropy (FA), and high-affinity RNA binding was found to require Zn coordination to both domains. HDX-MS of ZRANB2-2D with TRA2B RNA as well as two optimized RNA sequences that contain a single and double AGGUAA hexamer revealed additional protection from H/D exchange for ZRANB2 in the presence of RNA. Here, greater protection was observed for the second ZF of ZRANB2-2D, suggesting a larger effect on conformational dynamics. A model for zinc-mediated RNA binding of ZRANB2 is proposed.

2024-12-31·Autoimmunity

Identification the role of necroptosis in rheumatoid arthritis by WGCNA network

Article

作者: Yang, Mingfeng ; Wang, Yiwen ; Zhang, Bin ; Nian, Feige

Rheumatoid arthritis (RA) is the predominant manifestation of inflammatory arthritis, distinguished by an increasing burden of morbidity and mortality. The intricate interplay of genes and signalling pathways involved in synovial inflammation in patients with RA remains inadequately comprehended. This study aimed to ascertain the role of necroptosis in RA, as along with their associations with immune cell infiltration. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify central genes for RA. In this study, identified total of 28 differentially expressed genes (DEGs) were identified in RA. Utilising WGCNA, two co-expression modules were generated, with one module demonstrating the strongest correlation with RA. Through the integration of differential gene expression analysis, a total of 5 intersecting genes were discovered. These 5 hub genes, namely fused in sarcoma (FUS), transformer 2 beta homolog (TRA2B), eukaryotic translation elongation factor 2 (EEF2), cleavage and polyadenylation specific factor 6 (CPSF6) and signal transducer and activator of transcription 3 (STAT3) were found to possess significant diagnostic value as determined by receiver operating characteristic (ROC) curve analysis. The close association between the concentrations of various immune cells is anticipated to contribute to the diagnosis and treatment of RA. Furthermore, the infiltration of immune cells mentioned earlier is likely to exert a substantial influence on the initiation of this disease.

2024-12-01·RNA

Regulatory interplay between SR proteins governsCLK1kinase splice variants production

Article

作者: Delannoy, Aurelie ; Delannoy, Aurélie ; Toutant, Johanne ; Chabot, Benoit ; Shkreta, Lulzim

The CLK1 kinase phosphorylates SR proteins to modulate their splicing regulatory activity. Skipping of alternative exon 4 on theCLK1pre-mRNA produces a CLK1 variant lacking the catalytic site. Here, we aimed to understand how various SR proteins integrate into the regulatory program that controlsCLK1exon 4 splicing. Previously, we observed that the depletion of SRSF10 promoted the inclusion ofCLK1exon 4. Using the expression of tagged proteins and CRISPR/Cas9-mediated knockouts in HCT116 cells, we now identify TRA2β, TRA2α, SRSF4, SRSF5, SRSF7, SRSF8, and SRSF9 as activators of exon 4 inclusion. In contrast, SRSF3, SRSF10, and SRSF12 elicit exon 4 skipping. Using CRISPR/dCas13Rx and RNA immunoprecipitation assays, we map an enhancer in exon 4 interacting with TRA2β. Notably, CLK1 kinase inhibitors antagonized the repressor activity of HA-SRSF10, HA-SRSF12, and HA-SRSF3. Our results suggest thatCLK1exon 4 inclusion is determined primarily by a balance between the activities of TRA2 proteins and CLK-phosphorylated SRSF3. CLK-phosphorylated SRSF10 and SRSF12 would interact with TRA2 proteins to prevent their enhancer activity, allowing SRSF3 to enforce exon 4 skipping more efficiently. Our study provides insight into the complex regulatory network controlling the alternative splicing ofCLK1, which uses CLK1-mediated phosphorylation of SR proteins to regulate the inclusion of catalytic exon 4 inCLK1transcripts.