Transglutaminase‐2, RNA‐binding proteins and mitochondrial proteins selectively traffic to MDCK cell‐derived microvesicles following H‐Ras‐induced epithelial–mesenchymal transition

PROTEOMICS ◽  
2021 ◽  
pp. 2000221
Author(s):  
Adnan Shafiq ◽  
Wittaya Suwakulsiri ◽  
Alin Rai ◽  
Maoshan Chen ◽  
David W. Greening ◽  
...  
Keyword(s):  
Mdck Cell ◽  
Binding Proteins ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Rna Binding Proteins ◽  
Transglutaminase 2 ◽  
Mitochondrial Proteins ◽  
Mesenchymal Transition

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 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.

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