scholarly journals RNA binding protein RBM3 augments kissing loop formation with lncRNAs to enhance translational control

2021 ◽  
Author(s):  
Afreen Asif Ali Sayed ◽  
Sonali Choudhury ◽  
Dharmalingam Subramaniam ◽  
Sumedha Gunewardena ◽  
Sivapriya Ponnurangam ◽  
...  
Keyword(s):  
Translational Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Rna Binding Proteins ◽  
Tumor Xenograft ◽  
Rna Seq ◽  
Loop Formation ◽  
Mesenchymal Transition ◽  
Kissing Loop

Background and Aims: Translational regulation involve the coordinated actions of RNA binding proteins (RBPs) and non-coding RNAs. For efficient translation, the mRNA needs to be circularized. While RNA binding proteins and translation factors have been shown to regulate the circularization, the role of lncRNAs in the process is not yet defined. Methods: We first performed RNA-seq and RNA-immunoprecipitation coupled-Seq (RIP-Seq) to identify differentially expressed lncRNA and mRNA in RBM3 overexpressing cell lines. We manipulated lncRNA expression in the cells and determined effects on gene expression and cell viability and motility. The studies were confirmed in vivo in intestine specific RBM3 transgenic and RBM3 knockout mouse models. Results: In comparing the RNA-Seq and RIP-Seq datasets, we identified increased expression of lncRNA LSAMP-3 and Flii-1 that bind to RBM3. In addition, there was an increase in expression of epithelial mesenchymal transition and angiogenesis markers following RBM3 overexpression. Moreover, modeling studies suggest that these lncRNAs formed kissing-loop interactions on target mRNAs including transcripts that encode epithelial mesenchymal transition and angiogenesis. While RBM3 transgenic mice showed increased LSAMP-3 and Flii-1, this was reduced in the RBM3 knockout mice. Also, RBM3 overexpression increased tumor xenograft growth, which was suppressed by knockdown of the lncRNAs. Also, knockdown of endogenous RBM3 specifically in the intestine suppressed azoxymethane-dextran sodium sulfate driven colitis-associated cancers, with a corresponding reduction in the expression of lncRNAs and transcripts that encode epithelial mesenchymal transition and angiogenesis. Conclusion: We propose that RBPs such as RBM3 mediate their function through regulatory lncRNAs that enable circularization to control translation.

scholarly journals Identification of NOVA family proteins as novel β-catenin RNA-binding proteins that promote epithelial-mesenchymal transition

RNA Biology ◽  
2020 ◽  
Vol 17 (6) ◽  
pp. 881-891 ◽  
Author(s):  
Shulin Tang ◽  
Yurong Zhao ◽  
Xirong He ◽  
Jiahui Zhu ◽  
Shuang Chen ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Rna Binding Proteins ◽  
Mesenchymal Transition

scholarly journals RNA-Binding Proteins in Cancer: Functional and Therapeutic Perspectives

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2699
Author(s):  
Donghee Kang ◽  
Yerim Lee ◽  
Jae-Seon Lee
Keyword(s):  
Cancer Treatment ◽  
Genome Stability ◽  
Binding Proteins ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Rna Binding Proteins ◽  
Alternative Polyadenylation ◽  
Cancer Prognosis ◽  
Mesenchymal Transition ◽  
Cellular Phenotypes

RNA-binding proteins (RBPs) crucially regulate gene expression through post-transcriptional regulation, such as by modulating microRNA (miRNA) processing and the alternative splicing, alternative polyadenylation, subcellular localization, stability, and translation of RNAs. More than 1500 RBPs have been identified to date, and many of them are known to be deregulated in cancer. Alterations in the expression and localization of RBPs can influence the expression levels of oncogenes, tumor-suppressor genes, and genome stability-related genes. RBP-mediated gene regulation can lead to diverse cancer-related cellular phenotypes, such as proliferation, apoptosis, angiogenesis, senescence, and epithelial-mesenchymal transition (EMT)/invasion/metastasis. This regulation can also be associated with cancer prognosis. Thus, RBPs can be potential targets for the development of therapeutics for the cancer treatment. In this review, we describe the molecular functions of RBPs, their roles in cancer-related cellular phenotypes, and various approaches that may be used to target RBPs for cancer treatment.

scholarly journals Roles of Organellar RNA-Binding Proteins in Plant Growth, Development, and Abiotic Stress Responses

2020 ◽  
Vol 21 (12) ◽  
pp. 4548 ◽  
Author(s):  
Kwanuk Lee ◽  
Hunseung Kang
Keyword(s):  
Abiotic Stress ◽  
Plant Growth ◽  
Stress Responses ◽  
Translational Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Metabolism ◽  
Functional Roles ◽  
Growth Development

Organellar gene expression (OGE) in chloroplasts and mitochondria is primarily modulated at post-transcriptional levels, including RNA processing, intron splicing, RNA stability, editing, and translational control. Nucleus-encoded Chloroplast or Mitochondrial RNA-Binding Proteins (nCMRBPs) are key regulatory factors that are crucial for the fine-tuned regulation of post-transcriptional RNA metabolism in organelles. Although the functional roles of nCMRBPs have been studied in plants, their cellular and physiological functions remain largely unknown. Nevertheless, existing studies that have characterized the functions of nCMRBP families, such as chloroplast ribosome maturation and splicing domain (CRM) proteins, pentatricopeptide repeat (PPR) proteins, DEAD-Box RNA helicase (DBRH) proteins, and S1-domain containing proteins (SDPs), have begun to shed light on the role of nCMRBPs in plant growth, development, and stress responses. Here, we review the latest research developments regarding the functional roles of organellar RBPs in RNA metabolism during growth, development, and abiotic stress responses in plants.

scholarly journals RNA editing in cancer impacts mRNA abundance in immune response pathways

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Tracey W. Chan ◽  
Ting Fu ◽  
Jae Hoon Bahn ◽  
Hyun-Ik Jun ◽  
Jae-Hyung Lee ◽  
...  
Keyword(s):  
Immune Response ◽  
Rna Editing ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Rna Binding Proteins ◽  
Mrna Abundance ◽  
Mesenchymal Tumors ◽  
Mesenchymal Transition ◽  
Cancer Types ◽  
Experimental Validations

Abstract Background RNA editing generates modifications to the RNA sequences, thereby increasing protein diversity and shaping various layers of gene regulation. Recent studies have revealed global shifts in editing levels across many cancer types, as well as a few specific mechanisms implicating individual sites in tumorigenesis or metastasis. However, most tumor-associated sites, predominantly in noncoding regions, have unknown functional relevance. Results Here, we carry out integrative analysis of RNA editing profiles between epithelial and mesenchymal tumors, since epithelial-mesenchymal transition is a key paradigm for metastasis. We identify distinct editing patterns between epithelial and mesenchymal tumors in seven cancer types using TCGA data, an observation further supported by single-cell RNA sequencing data and ADAR perturbation experiments in cell culture. Through computational analyses and experimental validations, we show that differential editing sites between epithelial and mesenchymal phenotypes function by regulating mRNA abundance of their respective genes. Our analysis of RNA-binding proteins reveals ILF3 as a potential regulator of this process, supported by experimental validations. Consistent with the known roles of ILF3 in immune response, epithelial-mesenchymal differential editing sites are enriched in genes involved in immune and viral processes. The strongest target of editing-dependent ILF3 regulation is the transcript encoding PKR, a crucial player in immune and viral response. Conclusions Our study reports widespread differences in RNA editing between epithelial and mesenchymal tumors and a novel mechanism of editing-dependent regulation of mRNA abundance. It reveals the broad impact of RNA editing in cancer and its relevance to cancer-related immune pathways.

scholarly journals dSreg: a Bayesian model to integrate changes in splicing and RNA-binding protein activity

2019 ◽  
Vol 36 (7) ◽  
pp. 2134-2141
Author(s):  
Carlos Martí-Gómez ◽  
Enrique Lara-Pezzi ◽  
Fátima Sánchez-Cabo
Keyword(s):  
Bayesian Model ◽  
Binding Proteins ◽  
Rna Binding ◽  
Environmental Changes ◽  
Rna Binding Proteins ◽  
Gene Set Enrichment Analysis ◽  
Supplementary Information ◽  
Rna Seq ◽  
Protein Activity ◽  
Enrichment Methods

Abstract Motivation Alternative splicing (AS) is an important mechanism in the generation of transcript diversity across mammals. AS patterns are dynamically regulated during development and in response to environmental changes. Defects or perturbations in its regulation may lead to cancer or neurological disorders, among other pathological conditions. The regulatory mechanisms controlling AS in a given biological context are typically inferred using a two-step framework: differential AS analysis followed by enrichment methods. These strategies require setting rather arbitrary thresholds and are prone to error propagation along the analysis. Results To overcome these limitations, we propose dSreg, a Bayesian model that integrates RNA-seq with data from regulatory features, e.g. binding sites of RNA-binding proteins. dSreg identifies the key underlying regulators controlling AS changes and quantifies their activity while simultaneously estimating the changes in exon inclusion rates. dSreg increased both the sensitivity and the specificity of the identified AS changes in simulated data, even at low read coverage. dSreg also showed improved performance when analyzing a collection of knock-down RNA-binding proteins’ experiments from ENCODE, as opposed to traditional enrichment methods, such as over-representation analysis and gene set enrichment analysis. dSreg opens the possibility to integrate a large amount of readily available RNA-seq datasets at low coverage for AS analysis and allows more cost-effective RNA-seq experiments. Availability and implementation dSreg was implemented in python using stan and is freely available to the community at https://bitbucket.org/cmartiga/dsreg. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals First Identification of RNA-Binding Proteins That Regulate Alternative Exons in the Dystrophin Gene

2020 ◽  
Vol 21 (20) ◽  
pp. 7803
Author(s):  
Julie Miro ◽  
Anne-Laure Bougé ◽  
Eva Murauer ◽  
Emmanuelle Beyne ◽  
Dylan Da Cunha ◽  
...  
Keyword(s):  
Large Scale ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Dystrophin Gene ◽  
Rna Seq ◽  
Spatio Temporal ◽  
Dmd Gene ◽  
Shed Light

The Duchenne muscular dystrophy (DMD) gene has a complex expression pattern regulated by multiple tissue-specific promoters and by alternative splicing (AS) of the resulting transcripts. Here, we used an RNAi-based approach coupled with DMD-targeted RNA-seq to identify RNA-binding proteins (RBPs) that regulate splicing of its skeletal muscle isoform (Dp427m) in a human muscular cell line. A total of 16 RBPs comprising the major regulators of muscle-specific splicing events were tested. We show that distinct combinations of RBPs maintain the correct inclusion in the Dp427m of exons that undergo spatio-temporal AS in other dystrophin isoforms. In particular, our findings revealed the complex networks of RBPs contributing to the splicing of the two short DMD exons 71 and 78, the inclusion of exon 78 in the adult Dp427m isoform being crucial for muscle function. Among the RBPs tested, QKI and DDX5/DDX17 proteins are important determinants of DMD exon inclusion. This is the first large-scale study to determine which RBP proteins act on the physiological splicing of the DMD gene. Our data shed light on molecular mechanisms contributing to the expression of the different dystrophin isoforms, which could be influenced by a change in the function or expression level of the identified RBPs.

scholarly journals Translational Control of Cytochrome c by RNA-Binding Proteins TIA-1 and HuR

2006 ◽  
Vol 26 (8) ◽  
pp. 3295-3307 ◽  
Author(s):  
Tomoko Kawai ◽  
Ashish Lal ◽  
Xiaoling Yang ◽  
Stefanie Galban ◽  
Krystyna Mazan-Mamczarz ◽  
...  
Keyword(s):  
Er Stress ◽  
Translational Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Coding Region ◽  
Translation Rate ◽  
Translational Repressor

ABSTRACT Stresses affecting the endoplasmic reticulum (ER) globally modulate gene expression patterns by altering posttranscriptional processes such as translation. Here, we use tunicamycin (Tn) to investigate ER stress-triggered changes in the translation of cytochrome c, a pivotal regulator of apoptosis. We identified two RNA-binding proteins that associate with its ∼900-bp-long, adenine- and uridine-rich 3′ untranslated region (UTR): HuR, which displayed affinity for several regions of the cytochrome c 3′UTR, and T-cell-restricted intracellular antigen 1 (TIA-1), which preferentially bound the segment proximal to the coding region. HuR did not appear to influence the cytochrome c mRNA levels but instead promoted cytochrome c translation, as HuR silencing greatly diminished the levels of nascent cytochrome c protein. By contrast, TIA-1 functioned as a translational repressor of cytochrome c, with interventions to silence TIA-1 dramatically increasing cytochrome c translation. Following treatment with Tn, HuR binding to cytochrome c mRNA decreased, and both the presence of cytochrome c mRNA within actively translating polysomes and the rate of cytochrome c translation declined. Taken together, our data suggest that the translation rate of cytochrome c is determined by the opposing influences of HuR and TIA-1 upon the cytochrome c mRNA. Under unstressed conditions, cytochrome c mRNA is actively translated, but in response to ER stress agents, both HuR and TIA-1 contribute to lowering its biosynthesis rate. We propose that HuR and TIA-1 function coordinately to maintain precise levels of cytochrome c production under unstimulated conditions and to modify cytochrome c translation when damaged cells are faced with molecular decisions to follow a prosurvival or a prodeath path.

scholarly journals RNA-seq reveals the RNA binding proteins, Hfq and RsmA, play various roles in virulence, antibiotic production and genomic flux in Serratia sp. ATCC 39006

BMC Genomics ◽  
2013 ◽  
Vol 14 (1) ◽  
pp. 822 ◽  
Author(s):  
Nabil M Wilf ◽  
Adam J Reid ◽  
Joshua P Ramsay ◽  
Neil R Williamson ◽  
Nicholas J Croucher ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Antibiotic Production ◽  
Rna Seq
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