scholarly journals YBX1 Indirectly Targets Heterochromatin-Repressed Inflammatory Response-Related Apoptosis Genes through Regulating CBX5 mRNA

2020 ◽  
Vol 21 (12) ◽  
pp. 4453
Author(s):  
Andreas Kloetgen ◽  
Sujitha Duggimpudi ◽  
Konstantin Schuschel ◽  
Kebria Hezaveh ◽  
Daniel Picard ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Rna Binding ◽  
Binding Protein ◽  
Young Patients ◽  
Death Receptor ◽  
Posttranscriptional Control ◽  
Cellular Survival ◽  
Dna And Rna ◽  
Severe Impairment ◽  
Death Receptor Signaling

Medulloblastomas arise from undifferentiated precursor cells in the cerebellum and account for about 20% of all solid brain tumors during childhood; standard therapies include radiation and chemotherapy, which oftentimes come with severe impairment of the cognitive development of the young patients. Here, we show that the posttranscriptional regulator Y-box binding protein 1 (YBX1), a DNA- and RNA-binding protein, acts as an oncogene in medulloblastomas by regulating cellular survival and apoptosis. We observed different cellular responses upon YBX1 knockdown in several medulloblastoma cell lines, with significantly altered transcription and subsequent apoptosis rates. Mechanistically, PAR-CLIP for YBX1 and integration with RNA-Seq data uncovered direct posttranscriptional control of the heterochromatin-associated gene CBX5; upon YBX1 knockdown and subsequent CBX5 mRNA instability, heterochromatin-regulated genes involved in inflammatory response, apoptosis and death receptor signaling were de-repressed. Thus, YBX1 acts as an oncogene in medulloblastoma through indirect transcriptional regulation of inflammatory genes regulating apoptosis and represents a promising novel therapeutic target in this tumor entity.

At the Interface of Three Nucleic Acids: The Role of RNA-Binding Proteins and Poly(ADP-ribose) in DNA Repair

Acta Naturae ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 4-16 ◽  
Author(s):  
E. E. Alemasova ◽  
O. I. Lavrik
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Rna Granules ◽  
Dna And Rna ◽  
Cytoplasmic Rna

RNA-binding proteins (RBPs) regulate RNA metabolism, from synthesis to decay. When bound to RNA, RBPs act as guardians of the genome integrity at different levels, from DNA damage prevention to the post-transcriptional regulation of gene expression. Recently, RBPs have been shown to participate in DNA repair. This fact is of special interest as DNA repair pathways do not generally involve RNA. DNA damage in higher organisms triggers the formation of the RNA-like polymer - poly(ADP-ribose) (PAR). Nucleic acid-like properties allow PAR to recruit DNA- and RNA-binding proteins to the site of DNA damage. It is suggested that poly(ADP-ribose) and RBPs not only modulate the activities of DNA repair factors, but that they also play an important role in the formation of transient repairosome complexes in the nucleus. Cytoplasmic biomolecules are subjected to similar sorting during the formation of RNA assemblages by functionally related mRNAs and promiscuous RBPs. The Y-box-binding protein 1 (YB-1) is the major component of cytoplasmic RNA granules. Although YB-1 is a classic RNA-binding protein, it is now regarded as a non-canonical factor of DNA repair.

scholarly journals Identification of Ewing’s sarcoma protein as a G-quadruplex DNA- and RNA-binding protein

FEBS Journal ◽  
2011 ◽  
Vol 278 (6) ◽  
pp. 988-998 ◽  
Author(s):  
Kentaro Takahama ◽  
Katsuhito Kino ◽  
Shigeki Arai ◽  
Riki Kurokawa ◽  
Takanori Oyoshi
Keyword(s):  
Ewing’S Sarcoma ◽  
Rna Binding ◽  
Ewing's Sarcoma ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Quadruplex Dna ◽  
Dna And Rna ◽  
G Quadruplex ◽  
Dna And Rna Binding

scholarly journals The Value of Extracellular Cold-inducible RNA-binding Protein (eCIRP) in Predicting the Severity and Prognosis of Patients After Cardiac Arrest

2020 ◽  
Author(s):  
Ling Wang ◽  
Rui-Fang Li ◽  
Xiao-Lan Guan ◽  
Shuang-Shuang Liang ◽  
Ping Gong
Keyword(s):  
Inflammatory Response ◽  
Sofa Score ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Systemic Inflammatory Response ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Tnf Α ◽  
Neurological Prognosis

Abstract Background: Extracellular cold-inducible RNA-binding protein (eCIRP) acting as a novel damage-associated molecular pattern molecule promotes systemic inflammatory responses, including neuroinflammation in cerebral ischemia. We aimed to observe the changes of serum eCIRP and evaluate whether the increased serum eCIRP was associated with the severity and prognosis in patients with restoration of spontaneous circulation (ROSC).Methods: A total of 73 patients after ROSC were divided into non‑survivor (n = 48) and survivor (n = 25) groups based on 28‑day survival. Healthy volunteers (n = 25) were enrolled as controls. Serum eCIRP, procalcitonin (PCT), the pro-inflammatory mediators tumor necrosis factor (TNF)-α, interleukin-6 (IL)-6 and high mobility group protein (HMGB1), the neurological damage biomarkers neuron-specific enolase (NSE) and soluble protein 100β (S100β) were measured on days 1, 3 and 7 after ROSC. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation (APACHE II) were calculated concurrently. Cerebral performance category (CPC) scores on day 28 after ROSC were recorded.Results: Serum eCIRP, PCT, NSE and S100β, IL-6, TNF-α and HMGB1 were significantly increased within the first week after ROSC. The increased levels of eCIRP was positively correlated with IL-6, TNF-α, HMGB1, NSE, S100β, lactate, CPR time, SOFA score and APACHE II score after ROSC. Serum eCIRP on days 1, 3 and 7 after ROSC could predict 28-day mortality and neurological prognosis. Serum eCIRP on day 3 after ROSC had a biggest AUC [0.862 (95%CI: 0.741-0.941)] for 28-day mortality and a biggest AUC [0.807 (95%CI: 0.630-0.981)] for neurological prognosis. Conclusions: Systemic inflammatory response with increased serum eCIRP occurred in patients after ROSC. Increased eCIRP level was positively correlated with the aggravation of systemic inflammatory response and the severity after ROSC. Serum eCIRP serves as a potential predictor for 28-day mortality and poor neurological prognosis after ROSC.

scholarly journals IL-17 integrates multiple self-reinforcing, feed-forward mechanisms through the RNA binding protein Arid5a

2018 ◽  
Vol 11 (551) ◽  
pp. eaat4617 ◽  
Author(s):  
Nilesh Amatya ◽  
Erin E. Childs ◽  
J. Agustin Cruz ◽  
Felix E. Y. Aggor ◽  
Abhishek V. Garg ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Posttranscriptional Control ◽  
Feed Forward ◽  
Eukaryotic Translation ◽  
Interleukin 17A ◽  
Autoimmune Pathology ◽  
Eukaryotic Translation Initiation

Interleukin-17A (IL-17A) not only stimulates immunity to fungal pathogens but also contributes to autoimmune pathology. IL-17 is only a modest activator of transcription in experimental tissue culture settings. However, IL-17 controls posttranscriptional events that enhance the expression of target mRNAs. Here, we showed that the RNA binding protein (RBP) Arid5a (AT-rich interactive domain-containing protein 5a) integrated multiple IL-17–driven signaling pathways through posttranscriptional control of mRNA. IL-17 induced expression of Arid5a, which was recruited to the adaptor TRAF2. Arid5a stabilized IL-17–induced cytokine transcripts by binding to their 3′ untranslated regions and also counteracted mRNA degradation mediated by the endoribonuclease MCPIP1 (Regnase-1). Arid5a inducibly associated with the eukaryotic translation initiation complex and facilitated the translation of the transcription factors (TFs) IκBζ (Nfkbiz ) and C/EBPβ (Cebpb). These TFs in turn transactivated IL-17–dependent promoters. Together, these data indicated that Arid5a orchestrates a feed-forward amplification loop, which promoted IL-17 signaling by controlling mRNA stability and translation.

Sign in / Sign up

Export Citation Format

Share Document