A5064097084- RNA Research and Splicing
- RNA modifications and cancer
- interferon and immune responses
- Renal cell carcinoma treatment
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- Thyroid Cancer Diagnosis and Treatment
- Cancer-related Molecular Pathways
- RNA regulation and disease
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Renal and related cancers
- Hepatitis C virus research
- Cytomegalovirus and herpesvirus research
- MicroRNA in disease regulation
- NF-κB Signaling Pathways
- S100 Proteins and Annexins
- Molecular Biology Techniques and Applications
- Connective Tissue Growth Factor Research
- Cell death mechanisms and regulation
- Galectins and Cancer Biology
- Ferroptosis and cancer prognosis
King Faisal Specialist Hospital & Research Centre
2016-2025
Alfaisal University
2006-2019
Max Planck Institute for Molecular Biomedicine
2014
University of Minnesota Medical Center
2011
Minneapolis Institute of Arts
2011
King Saud University
2011
Cleveland Clinic
2000-2009
Cleveland Clinic Lerner College of Medicine
2004
The University of Tokyo
1997
Kanazawa Medical University
1997
ABSTRACT Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently resistant to the antiviral alpha interferon (IFN). The HCV nonstructural 5A (NS5A) protein has been implicated in resistance many studies. NS5A antagonizes IFN response vitro, and one mechanism via inhibition key IFN-induced enzyme, double-stranded-RNA-activated kinase (PKR). In present study we determined if uses other strategies subvert system. Expression full-length proteins from patients who...
Adenylate/uridylate-rich element (ARE)-mediated mRNA turnover is an important regulatory component of gene expression for innate and specific immunity, in the hematopoietic system, cellular growth regulation, many other processes. This diversity reflected distribution AREs human genome, which we have established as a database more than 900 ARE-containing genes that may utilize means controlling levels. The p38 mitogen-activated protein kinase (MAP kinase) pathway has been implicated...
ABSTRACT Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently resistant to the antiviral alpha interferon (IFN). We have recently found that HCV NS5A protein induces expression proinflammatory chemokine IL-8 partially inhibit actions IFN in vitro. To extend these observations, present study we examined relationship between levels serum, infection, and biochemical response therapy. Levels were significantly elevated 132 HCV-infected patients compared 32 normal...
Sunitinib is an antiangiogenic therapy given as a first-line treatment for renal cell carcinoma (RCC). While improves progression-free survival, most patients relapse. We hypothesized that patient relapse can stem from the development of lymphatic network driven by production main growth factor endothelial cells, VEGFC. In this study, we found sunitinib stimulate vegfc gene transcription and increase VEGFC mRNA half-life. addition, activated p38 MAPK, which resulted in upregulation/activity...
The Adenylate Uridylate (AU)-Rich Element Database, ARED-mRNA version 2.0, contains information not present in the previous ARED. This includes additional data entries, new and links to Unigene, LocusLink, RefSeq records mouse homologue data. An ARE consensus sequence specific 3'UTR is basis of ARED that demonstrated two important findings: (i) AREs are a large, previously unrecognized set human mRNAs; (ii) ARE-mRNAs encode proteins diverse functions which largely involved early transient...
Cytomegalovirus (CMV) infection induced interleukin-8 (IL-8) gene transcription in a human monocytic cell line, THP-1 cells, leading to IL-8 secretion. The functional analysis of the revealed that both AP-1- and NF-kappaB factor-binding elements were involved conferring responsiveness CMV. Moreover, electrophoretic mobility shift assays demonstrated CMV formation AP-1 complexes. These results suggest activates these transcriptional factors, resulting expression.
Beta-catenin plays an essential role in several biological events including cell fate determination, proliferation, and transformation. Here we report that beta-catenin is encoded by a labile transcript whose half-life prolonged Wnt phosphatidylinositol 3-kinase-AKT signaling. AKT phosphorylates the mRNA decay-promoting factor KSRP at unique serine residue, induces its association with multifunctional protein 14-3-3, prevents interaction exoribonucleolytic complex exosome. This impairs...
ARED Organism represents the expansion of adenylate uridylate (AU)-rich element (ARE)-containing human mRNA database into transcriptomes mouse and rat. As a result, we performed quantitative assessment ARE conservation in human, rat transcripts. We found that significant proportion ( approximately 25%) genes differ their patterns from ARED-Integrated, another updated expanded version ARED, is compilation versions 1.0 to 3.0 4.0 devoted mRNAs. Thus, ARED-Integrated ARED-Organism databases,...
Interferon (IFN) exhibits a potent antiviral activity in vitro and plays major role the early defense against viruses. Like IFN, proinflammatory chemokine, interleukin (IL)-8, is induced by viruses appears circulation during viral infections. In an cytopathic effect assay for we found that IL-8 can inhibit IFN-alpha dose-dependent manner. This action was reversed specific monoclonal antibodies to IL-8. The chemokine able attenuate IFN-mediated inhibition of replication as determined...
The RNA-binding protein, HuR, is involved in the stabilization of AU-rich element-containing mRNAs with products that are cell-cycle progression, cell differentiation and inflammation.We show there multiple polyadenylation variants HuR mRNA differ their abundance, using both bioinformatics experimental approaches.A variant distal poly(A) signal a rare transcript harbors functional elements (ARE) 3'UTR.A minimal 60-nt region, but not mutant form, fused to reporter-3'UTR constructs was able...
Defects in AU-rich elements (ARE)-mediated posttranscriptional control can lead to several abnormal processes that underlie carcinogenesis. Here, we performed a systematic analysis of ARE-mRNA expression across multiple cancer types. First, the ARE database (ARED) was intersected with The Cancer Genome Atlas databases and others. A large set ARE-mRNAs over-represented and, unlike non-ARE-mRNAs, correlated reversed balance RNA-binding proteins tristetraprolin (TTP, ZFP36) HuR (ELAVL1). Serial...
Here we present an updated version of the AU-Rich Element Database (ARED-Plus) that is freely available at http://brp.kfshrc.edu.sa/ared. AREs are conserved sequence elements were first discovered in 3′UTR mammalian transcripts. Over past years, compiled a series ARE databases revealed extent and wide distribution ARE-containing genes. For this update, adopted optimized search algorithm with improved specificity sensitivity selection. The designation different clusters was simplified by...
Adenylate-uridylate (AU)-rich elements (AREs) are sequence instability that known to be located in the 3' untranslated regions (UTR) thousands of human transcripts. AREs regulate expression many genes at post-transcriptional level, and they essential for normal cellular functions. We conducted a transcriptome-wide screen found most abundant introns, with up 25% introns containing corresponding 58% genes. Clustering studies ARE size, complexity, distribution revealed that, longer two or more...
AU-rich elements (AREs), located in the 3′-untranslated region of unstable cytokine and chemokine mRNAs, promote rapid decay otherwise stable mRNAs may mediate selective mRNA stabilization response to stimulation with interleukin-1 (IL-1). AREs vary considerably, however, both size sequence context. To assess heterogeneity involved control stability by ARE motifs, human sequences from IL-1α-stimulated HEK293 cells T98G were screened for either instability or using cDNA (950 containing...
The activities of RNA-binding proteins are perturbed in several pathological conditions, including cancer. These include tristetraprolin (TTP, ZFP36) and HuR (ELAVL1), which respectively promote the decay or stability adenylate-uridylate-rich (AU-rich) mRNAs. Here, we demonstrated that increased stabilization subsequent over-expression mRNA were coupled to TTP deficiency. findings observed breast cancer cell lines with an invasive phenotype further confirmed ZFP36-knockout mouse fibroblasts....
UU and UA dinucleotides are rare in mammalian genes may offer natural selection against endoribonuclease-mediated mRNA decay. This study hypothesized that reducing (UW) the mRNA-coding sequence, including codons dicodon boundaries, promote resistance to decay, thereby increasing protein production. Indeed, expression from UW-reduced coding regions of enhanced green fluorescent (EGFP), luciferase, interferon-α, hepatitis B surface antigen (HBsAg) was higher when compared wild-type expression....
Abstract Background Long-read whole genome sequencing (lrWGS) has the potential to address technical limitations of exome in ways not possible by short-read WGS. However, its utility autosomal recessive Mendelian diseases is largely unknown. Methods In a cohort 34 families which suspected remained undiagnosed sequencing, lrWGS was performed on Pacific Bioscience Sequel IIe platform. Results Likely causal variants were identified 13 (38%) cohort. These include (1) homozygous splicing SV TYMS...
Hepatitis C virus (HCV) infection induces the alpha-chemokine interleukin-8 (CXCL-8), which is regulated at levels of transcription and mRNA stability. In current study, CXCL-8 regulation by double-stranded (ds)RNA pathways was analyzed in context HCV infection. A constitutively active mutant retinoic acid-inducible gene I (RIG-I), RIG-N, activated transcription. Promoter mutagenesis experiments indicated that NF-kappaB interferon (IFN)-stimulated response element (ISRE) binding sites were...