A global analysis on the differential regulation of RNA binding proteins (RBPs) by TNF–α as potential modulators of metabolic syndromes

Tumour necrosis factor (TNF)-α mRNA contains an AU-rich element (ARE) in its 3′ untranslated region (3′UTR), which determines its half-life and translational efficiency. In unstimulated macrophages, TNF-α mRNA is repressed translationally, and becomes efficiently translated upon cell activation. Gel retardation experiments and screening of a macrophage cDNA expression library with the TNF-α ARE allowed the identification of TIA-1-related protein (TIAR), T-cell intracellular antigen-1 (TIA-1) and tristetraprolin (TTP) as TNF-α ARE-binding proteins. Whereas TIAR and TIA-1 bind the TNF-α ARE independently of the activation state of macrophages, the TTP-ARE complex is detectable upon stimulation with lipopolysaccharide (LPS). Moreover, treatment of LPS-induced macrophage extracts with phosphatase significantly abrogates TTP binding to the TNF-α ARE, indicating that TTP phosphorylation is required for ARE binding. Carballo, Lai and Blackshear [(1998) Science 281, 1001–1005] showed that TTP was a TNF-α mRNA destabilizer. In contrast, TIA-1, and most probably TIAR, acts as a TNF-α mRNA translational silencer. A two-hybrid screening with TIAR and TIA-1 revealed the capacity of these proteins to interact with other RNA-binding proteins. Interestingly, TIAR and TIA-1 are not engaged in the same interaction, indicating for the first time that TIAR and TIA-1 can be functionally distinct. These findings also suggest that ARE-binding proteins interact with RNA as multimeric complexes, which might define their function and their sequence specificity.

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Cloning and characterization of three cDNAs encoding chloroplast RNA-binding proteins from barley ( Hordeum vulgare L.): differential regulation of expression by light and plastid development

Current Genetics ◽

10.1007/s002940050488 ◽

1999 ◽

Vol 36 (3) ◽

pp. 173-181 ◽

Cited By ~ 17

Author(s):

Yuri Churin ◽

Wolfgang R. Hess ◽

Thomas Börner

Keyword(s):

Hordeum Vulgare ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Differential Regulation ◽

Hordeum Vulgare L ◽

Plastid Development ◽

Regulation Of Expression ◽

Chloroplast Rna

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Integrated Analysis of RNA-Binding Proteins in Glioma

Cancers ◽

10.3390/cancers12040892 ◽

2020 ◽

Vol 12 (4) ◽

pp. 892 ◽

Cited By ~ 2

Author(s):

Zhixing Wang ◽

Wanjun Tang ◽

Jiangang Yuan ◽

Boqin Qiang ◽

Wei Han ◽

...

Keyword(s):

Gene Ontology ◽

Survival Analysis ◽

Cell Growth ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Global Analysis ◽

The Cancer Genome Atlas ◽

Integrated Analysis ◽

Genome Atlas

RNA-binding proteins (RBPs) play important roles in many cancer types. However, RBPs have not been thoroughly and systematically studied in gliomas. Global analysis of the functional impact of RBPs will provide a better understanding of gliomagenesis and new insights into glioma therapy. In this study, we integrated a list of the human RBPs from six sources—Gerstberger, SONAR, Gene Ontology project, Poly(A) binding protein, CARIC, and XRNAX—which covered 4127 proteins with RNA-binding activity. The RNA sequencing data were downloaded from The Cancer Genome Atlas (TCGA) (n = 699) and Chinese Glioma Genome Atlas (CGGA) (n = 325 + 693). We examined the differentially expressed genes (DEGs) using the R package DESeq2, and constructed a weighted gene co-expression network analysis (WGCNA) of RBPs. Furthermore, survival analysis was also performed based on the univariate and multivariate Cox proportional hazards regression models. In the WGCNA analysis, we identified a key module involved in the overall survival (OS) of glioblastomas. Survival analysis revealed eight RBPs (PTRF, FNDC3B, SLC25A43, ZC3H12A, LRRFIP1, HSP90B1, HSPA5, and BNC2) are significantly associated with the survival of glioblastoma patients. Another 693 patients within the CGGA database were used to validate the findings. Additionally, 3564 RBPs were classified into canonical and non-canonical RBPs depending on the domains that they contain, and non-canonical RBPs account for the majority (72.95%). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that some non-canonical RBPs may have functions in glioma. Finally, we found that the knockdown of non-canonical RBPs, PTRF, or FNDC3B can alone significantly inhibit the proliferation of LN229 and U251 cells. Simultaneously, RNA Immunoprecipitation (RIP) analysis indicated that PTRF may regulate cell growth and death- related pathways to maintain tumor cell growth. In conclusion, our findings presented an integrated view to assess the potential death risks of glioblastoma at a molecular level, based on the expression of RBPs. More importantly, we identified non-canonical RNA-binding proteins PTRF and FNDC3B, showing them to be potential prognostic biomarkers for glioblastoma.

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