scholarly journals Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state

2019 ◽  
Vol 116 (37) ◽  
pp. 18619-18628 ◽  
Author(s):  
Jaewon Song ◽  
Sanghyun Lee ◽  
Dong-Yeon Cho ◽  
Sungwon Lee ◽  
Hyewon Kim ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Rna Processing ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Transcriptome Profiling ◽  
Loss Of Function ◽  
Antiviral Genes ◽  
Cellular Antiviral Response ◽  
Infected Cells

RNA represents a pivotal component of host–pathogen interactions. Human cytomegalovirus (HCMV) infection causes extensive alteration in host RNA metabolism, but the functional relationship between the virus and cellular RNA processing remains largely unknown. Through loss-of-function screening, we show that HCMV requires multiple RNA-processing machineries for efficient viral lytic production. In particular, the cellular RNA-binding protein Roquin, whose expression is actively stimulated by HCMV, plays an essential role in inhibiting the innate immune response. Transcriptome profiling revealed Roquin-dependent global down-regulation of proinflammatory cytokines and antiviral genes in HCMV-infected cells. Furthermore, using cross-linking immunoprecipitation (CLIP)-sequencing (seq), we identified IFN regulatory factor 1 (IRF1), a master transcriptional activator of immune responses, as a Roquin target gene. Roquin reduces IRF1 expression by directly binding to its mRNA, thereby enabling suppression of a variety of antiviral genes. This study demonstrates how HCMV exploits host RNA-binding protein to prevent a cellular antiviral response and offers mechanistic insight into the potential development of CMV therapeutics.

scholarly journals Transcriptome-Wide Identification of RNA Targets of Arabidopsis SERINE/ARGININE-RICH45 Uncovers the Unexpected Roles of This RNA Binding Protein in RNA Processing

2015 ◽  
Vol 27 (12) ◽  
pp. 3294-3308 ◽  
Author(s):  
Denghui Xing ◽  
Yajun Wang ◽  
Michael Hamilton ◽  
Asa Ben-Hur ◽  
Anireddy S.N. Reddy
Keyword(s):  
Rna Processing ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Rna Targets

scholarly journals LncRNA SNHG1 and RNA Binding Protein hnRNPL form a Complex and Coregulate CDH1 to Boost the Growth and Metastasis of Prostate Cancer

2020 ◽  
Author(s):  
Xiao Tan ◽  
Wen-Bin Chen ◽  
Dao-Jun Lv ◽  
Tao-Wei Yang ◽  
Kai-Hui Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Binding Protein ◽  
Expression Profiles ◽  
Mrna Level ◽  
Rna Binding Protein ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Background: The interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of SNHG1, an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, the underlying mechanism between SNHG1 and RBPs in tumors remains to be explored, especially in prostate cancer (PCa).Methods：SNHG1 expression profiles in PCa were determined through the analysis of TCGA data and tissue microarray at the mRNA level. Gain- and loss-of-function experiments were performed to investigate the biological role of SNHG1 in PCa initiation and progression. RNA-seq, immunoblotting, RNA pull-down and RNA immunoprecipitation analyses were utilized to clarify potential pathways with which SNHG1 might be involved. Finally, rescue experiments were carried out to further confirm this mechanism.Results: We found that SNHG1 was dominantly expressed in the nuclei of PCa cells and significantly upregulated in PCa patients. The higher expression level of SNHG1 was dramatically correlated with tumor metastasis and patient survival. Functionally, overexpression of SNHG1 in PCa cells induced epithelial–mesenchymal transition (EMT), accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation and migration, as well as accelerated xenograft tumor growth, were observed in SNHG1-overexpressing PCa cells, while opposite effects were achieved in SNHG1-silenced cells. Mechanistically, SNHG1 competitively interacted with hnRNPL to impair the translation of protein E-cadherin, thus activating the effect of SNHG1 on the EMT pathway, eventually promoting the metastasis of PCa. Conclusion: Our findings demonstrate that SNHG1 is a positive regulator of EMT activation through the SNHG1-hnRNPL-CDH1 axis. SNHG1 may serve as a novel potential therapeutic target for PCa.

scholarly journals Nuclear depletion of RNA binding protein ELAVL3 (HuC) in sporadic and familial amyotrophic lateral sclerosis

2021 ◽  
Author(s):  
Sandra Diaz-Garcia ◽  
Vivian I. Ko ◽  
Sonia Vazquez-Sanchez ◽  
Ruth Chia ◽  
Olubankole Aladesuyi Arogundade ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Loss Of Function ◽  
Cryptic Exon ◽  
Protein Levels ◽  
Sporadic Als ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis is a progressive fatal neurodegenerative disease caused by loss of motor neurons and characterized neuropathologically in almost all cases by nuclear depletion and cytoplasmic aggregation of TDP-43, a nuclear RNA binding protein (RBP). We identified ELAVL3 as one of the most downregulated genes in our transcriptome profiles of laser captured microdissection of motor neurons from sporadic ALS nervous systems and the top dysregulated RBPs. Neuropathological characterizations showed ELAVL3 nuclear depletion in a great percentage of remnant motor neurons, sometimes accompanied by cytoplasmic accumulations. These abnormalities were common in sporadic cases with and without intermediate expansions in ATXN2 and familial cases carrying mutations in C9orf72 and SOD1. Depletion of ELAVL3 occurred at both the RNA and protein levels and a short protein isoform was identified but it is not related to a TDP-43-dependent cryptic exon in intron 3. Strikingly, ELAVL3 abnormalities were more frequent than TDP-43 abnormalities and occurred in motor neurons still with normal nuclear TDP-43 present, but all neurons with abnormal TDP-43 also had abnormal ELAVL3. In a neuron-like cell culture model using SH-SY5Y cells, ELAVL3 mislocalization occurred weeks before TDP-43 abnormalities were seen. We interrogated genetic databases but did not identify association of ELAVL3 genetic structure associated with ALS. Taken together, these findings suggest that ELAVL3 is an important RBP in ALS pathogenesis acquired early and the neuropathological data suggest it is involved by loss of function rather than cytoplasmic toxicity.

Abstract 204: Molecular function of the RNA binding protein EWS in RNA processing

2012 ◽  
Author(s):  
Bethsaida I. Nieves ◽  
Shuang Niu ◽  
Dedeepya Vaka ◽  
Julia Salzman ◽  
Patrick Brown ◽  
...  
Keyword(s):  
Rna Processing ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Molecular Function

scholarly journals RNA-binding protein IGF2BP2 enhances circ_0000745 abundancy and promotes aggressiveness and stemness of ovarian cancer cells via the microRNA-3187-3p/ERBB4/PI3K/AKT axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shengtan Wang ◽  
Zaihong Li ◽  
Genhai Zhu ◽  
Lan Hong ◽  
Chunyan Hu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Circular Rnas ◽  
Ovarian Cancer Cells ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Repressive Effect

Abstract Background Circular RNAs (circRNAs) are increasingly recognized as important regulators in cancer including ovarian cancer (OC). This work focuses on the effects of circ_0000745 on the OC development of and molecules involved. Methods Expression of circ_0000745 in collected OC tissues and the acquired OC cell lines was examined by RT-qPCR. The stability of circ_0000745 in cells was examined by RNase R treatment. The target transcripts interacted with circ_0000745 were predicted using bioinformatic systems. Gain- and loss-of-function studies of circ_0000745, microRNA (miR)-3187-3p and erb-b2 receptor tyrosine kinase 4 (ERBB4) were conducted to determine their functions on proliferation, migration, invasion and stem cell property of OC cells. Results Circ_0000745 and ERBB4 were abundantly expressed while miR-3187-3p was poorly expressed in OC tissues and cells. Circ_0000745 sequestered miR-3187-3p and blocked its repressive effect on ERBB4. Downregulation of circ_0000745 reduced proliferation, aggressiveness, epithelial-mesenchymal transition, and stemness of SK-OV-3 cells, but this reduction was blocked upon miR-3187-3p inhibition or ERBB4 upregulation. By contrast, artificial induction of circ_0000745 upregulation, miR-3187-3p upregulation and ERBB4 downregulation led to inverse trends in ES-2 cells. ERBB4 promoted the phosphorylation of the PI3K/AKT signaling pathway. An RNA binding protein IGF2BP2 was found to circ_0000745 bind to and promote its expression and stability. Conclusion This study demonstrated that circ_0000745 upregulated by IGF2BP2 promotes aggressiveness and stemness of OC cells through a miR-3187-3p/ERBB4/PI3K/AKT axis. Circ_0000745 may serve as a promising target for OC treatment.

scholarly journals FASTKD2 is an RNA-binding protein required for mitochondrial RNA processing and translation

RNA ◽  
2015 ◽  
Vol 21 (11) ◽  
pp. 1873-1884 ◽  
Author(s):  
Johannes Popow ◽  
Anne-Marie Alleaume ◽  
Tomaz Curk ◽  
Thomas Schwarzl ◽  
Sven Sauer ◽  
...  
Keyword(s):  
Rna Processing ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mitochondrial Rna

scholarly journals The Chloroplast RNA Binding Protein CP31A Has a Preference for mRNAs Encoding the Subunits of the Chloroplast NAD(P)H Dehydrogenase Complex and Is Required for Their Accumulation

2020 ◽  
Vol 21 (16) ◽  
pp. 5633
Author(s):  
Benjamin Lenzen ◽  
Thilo Rühle ◽  
Marie-Kristin Lehniger ◽  
Ayako Okuzaki ◽  
Mathias Labs ◽  
...  
Keyword(s):  
Rna Processing ◽  
Gene Expression Analysis ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Blot Hybridization ◽  
Rna Binding Protein ◽  
Target Range ◽  
Rna Targets ◽  
Chloroplast Rna

Chloroplast RNA processing requires a large number of nuclear-encoded RNA binding proteins (RBPs) that are imported post-translationally into the organelle. Most of these RBPs are highly specific for one or few target RNAs. By contrast, members of the chloroplast ribonucleoprotein family (cpRNPs) have a wider RNA target range. We here present a quantitative analysis of RNA targets of the cpRNP CP31A using digestion-optimized RNA co-immunoprecipitation with deep sequencing (DO-RIP-seq). This identifies the mRNAs coding for subunits of the chloroplast NAD(P)H dehydrogenase (NDH) complex as main targets for CP31A. We demonstrate using whole-genome gene expression analysis and targeted RNA gel blot hybridization that the ndh mRNAs are all down-regulated in cp31a mutants. This diminishes the activity of the NDH complex. Our findings demonstrate how a chloroplast RNA binding protein can combine functionally related RNAs into one post-transcriptional operon.

scholarly journals R-loop resolution promotes co-transcriptional chromatin silencing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Congyao Xu ◽  
Zhe Wu ◽  
Hong-Chao Duan ◽  
Xiaofeng Fang ◽  
Guifang Jia ◽  
...  
Keyword(s):  
Dna Damage ◽  
Rna Processing ◽  
Antisense Transcript ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Arabidopsis Genome ◽  
Nascent Transcript ◽  
Genome Regulation ◽  
Processing Factors

AbstractRNA-mediated chromatin silencing is central to genome regulation in many organisms. However, how nascent non-coding transcripts regulate chromatin is poorly understood. Here, through analysis of Arabidopsis FLC, we show that resolution of a nascent-transcript-induced R-loop promotes chromatin silencing. Stabilization of an antisense-induced R-loop at the 3′ end of FLC enables an RNA binding protein FCA, with its direct partner FY/WDR33 and other 3′-end processing factors, to polyadenylate the nascent antisense transcript. This clears the R-loop and recruits the chromatin modifiers demethylating H3K4me1. FCA immunoprecipitates with components of the m6A writer complex, and m6A modification affects dynamics of FCA nuclear condensates, and promotes FLC chromatin silencing. This mechanism also targets other loci in the Arabidopsis genome, and consistent with this fca and fy are hypersensitive to a DNA damage-inducing drug. These results show how modulation of R-loop stability by co-transcriptional RNA processing can trigger chromatin silencing.

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