ADAR1 RNA editing regulates endothelial cell functions via the MDA-5 RNA sensing signaling pathway

The RNA-sensing signaling pathway has been well studied as an essential antiviral mechanism of innate immunity. However, its role in non-infected cells is yet to be thoroughly characterized. Here, we demonstrated that the RNA sensing signaling pathway also reacts to the endogenous cellular RNAs in endothelial cells (ECs), and this reaction is regulated by the RNA-editing enzyme ADAR1. Cellular RNA sequencing analysis showed that EC RNAs endure extensive RNA editing, especially in the RNA transcripts of short interspersed nuclear elements. The EC-specific deletion of ADAR1 dramatically reduced the editing level on short interspersed nuclear element RNAs, resulting in newborn death in mice with damage evident in multiple organs. Genome-wide gene expression analysis revealed a prominent innate immune activation with a dramatically elevated expression of interferon-stimulated genes. However, blocking the RNA sensing signaling pathway by deletion of the cellular RNA receptor MDA-5 prevented interferon-stimulated gene expression and rescued the newborn mice from death. This evidence demonstrated that the RNA-editing/RNA-sensing signaling pathway dramatically modulates EC function, representing a novel molecular mechanism for the regulation of EC functions.

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Epitranscriptomic profiling across cell types reveals associations between APOBEC1-mediated RNA editing, gene expression outcomes, and cellular function

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1714227114 ◽

2017 ◽

Vol 114 (50) ◽

pp. 13296-13301 ◽

Cited By ~ 18

Author(s):

Violeta Rayon-Estrada ◽

Dewi Harjanto ◽

Claire E. Hamilton ◽

Yamina A. Berchiche ◽

Emily Conn Gantman ◽

...

Keyword(s):

Gene Expression ◽

Rna Editing ◽

Rna Stability ◽

Cell Types ◽

Fine Tuning ◽

Mrna Editing ◽

Cellular Processes ◽

Small Set ◽

Functional Relevance ◽

Editing Enzyme

Epitranscriptomics refers to posttranscriptional alterations on an mRNA sequence that are dynamic and reproducible, and affect gene expression in a similar way to epigenetic modifications. However, the functional relevance of those modifications for the transcript, the cell, and the organism remain poorly understood. Here, we focus on RNA editing and show that Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-1 (APOBEC1), together with its cofactor RBM47, mediates robust editing in different tissues. The majority of editing events alter the sequence of the 3′UTR of targeted transcripts, and we focus on one cell type (monocytes) and on a small set of highly edited transcripts within it to show that editing alters gene expression by modulating translation (but not RNA stability or localization). We further show that specific cellular processes (phagocytosis and transendothelial migration) are enriched for transcripts that are targets of editing and that editing alters their function. Finally, we survey bone marrow progenitors and demonstrate that common monocyte progenitor cells express high levels of APOBEC1 and are susceptible to loss of the editing enzyme. Overall, APOBEC1-mediated transcriptome diversification is required for the fine-tuning of protein expression in monocytes, suggesting an epitranscriptomic mechanism for the proper maintenance of homeostasis in innate immune cells.

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The C. elegans neural editome reveals an ADAR target mRNA required for proper chemotaxis

eLife ◽

10.7554/elife.28625 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 16

Author(s):

Sarah N Deffit ◽

Brian A Yee ◽

Aidan C Manning ◽

Suba Rajendren ◽

Pranathi Vadlamani ◽

...

Keyword(s):

Gene Expression ◽

Caenorhabditis Elegans ◽

Rna Editing ◽

Regulatory Elements ◽

Neural Cells ◽

Neuronal Function ◽

C Elegans ◽

Altered Gene Expression ◽

Altered Gene ◽

Editing Enzyme

ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. Caenorhabditis elegans lacking ADARs exhibit reduced chemotaxis, but the targets responsible for this phenotype remain unknown. To identify critical neural ADAR targets in C. elegans, we performed an unbiased assessment of the effects of ADR-2, the only A-to-I editing enzyme in C. elegans, on the neural transcriptome. Development and implementation of publicly available software, SAILOR, identified 7361 A-to-I editing events across the neural transcriptome. Intersecting the neural editome with adr-2 associated gene expression changes, revealed an edited mRNA, clec-41, whose neural expression is dependent on deamination. Restoring clec-41 expression in adr-2 deficient neural cells rescued the chemotaxis defect, providing the first evidence that neuronal phenotypes of ADAR mutants can be caused by altered gene expression.

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Apolipoprotein B mRNA Editing Enzyme, Catalytic Polypeptide-Like Gene Expression, RNA Editing, and MicroRNAs Regulation

MicroRNA and Cancer - Methods in Molecular Biology ◽

10.1007/978-1-4939-7435-1_5 ◽

2017 ◽

pp. 75-81 ◽

Cited By ~ 1

Author(s):

Wei Cao ◽

Wei Wu

Keyword(s):

Gene Expression ◽

Rna Editing ◽

Apolipoprotein B ◽

Mrna Editing ◽

Editing Enzyme

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PI3K signaling Pathway gene expression analysis in cumulus cells by Real-Time PCR

10.26226/morressier.573c1511d462b80296c982f0 ◽

2016 ◽

Author(s):

Paolo Giovanni Artini

Keyword(s):

Gene Expression ◽

Real Time ◽

Signaling Pathway ◽

Real Time Pcr ◽

Gene Expression Analysis ◽

Cumulus Cells ◽

Pi3k Signaling ◽

Pathway Gene ◽

Pi3k Signaling Pathway ◽

Signaling Pathway Gene

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Dynamic DNA structure states interact with the RNA editing enzyme ADAR1 to modulate fear extinction memory

10.26226/morressier.5ebd45acffea6f735881ae71 ◽

2020 ◽

Author(s):

Paul Robert Marshall

Keyword(s):

Rna Editing ◽

Dna Structure ◽

Fear Extinction ◽

Extinction Memory ◽

Editing Enzyme

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Faculty Opinions recommendation of TRIBE: Hijacking an RNA-Editing Enzyme to Identify Cell-Specific Targets of RNA-Binding Proteins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726264062.793520489 ◽

2016 ◽

Author(s):

Michael B Yaffe

Keyword(s):

Rna Editing ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Editing Enzyme

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A New Approach for Predicting the Value of Gene Expression: Two-way Collaborative Filtering

Current Bioinformatics ◽

10.2174/1574893614666190126144139 ◽

2019 ◽

Vol 14 (6) ◽

pp. 480-490 ◽

Cited By ~ 1

Author(s):

Tuncay Bayrak ◽

Hasan Oğul

Keyword(s):

Gene Expression ◽

Regression Model ◽

Collaborative Filtering ◽

High Throughput Sequencing ◽

Mean Squared Error ◽

Experimental Studies ◽

Kernel Functions ◽

Feature Representation ◽

Sequencing Analysis ◽

Computational Systems Biology

Background: Predicting the value of gene expression in a given condition is a challenging topic in computational systems biology. Only a limited number of studies in this area have provided solutions to predict the expression in a particular pattern, whether or not it can be done effectively. However, the value of expression for the measurement is usually needed for further meta-data analysis. Methods: Because the problem is considered as a regression task where a feature representation of the gene under consideration is fed into a trained model to predict a continuous variable that refers to its exact expression level, we introduced a novel feature representation scheme to support work on such a task based on two-way collaborative filtering. At this point, our main argument is that the expressions of other genes in the current condition are as important as the expression of the current gene in other conditions. For regression analysis, linear regression and a recently popularized method, called Relevance Vector Machine (RVM), are used. Pearson and Spearman correlation coefficients and Root Mean Squared Error are used for evaluation. The effects of regression model type, RVM kernel functions, and parameters have been analysed in our study in a gene expression profiling data comprising a set of prostate cancer samples. Results: According to the findings of this study, in addition to promising results from the experimental studies, integrating data from another disease type, such as colon cancer in our case, can significantly improve the prediction performance of the regression model. Conclusion: The results also showed that the performed new feature representation approach and RVM regression model are promising for many machine learning problems in microarray and high throughput sequencing analysis.

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Bv8-Like Toxin from the Frog Venom of Amolops jingdongensis Promotes Wound Healing via the Interleukin-1 Signaling Pathway

Toxins ◽

10.3390/toxins12010015 ◽

2019 ◽

Vol 12 (1) ◽

pp. 15 ◽

Cited By ~ 1

Author(s):

Jiajia Chang ◽

Xiaoqin He ◽

Jingmei Hu ◽

Peter Muiruri Kamau ◽

Ren Lai ◽

...

Keyword(s):

Wound Healing ◽

Signaling Pathway ◽

Wide Spectrum ◽

Interleukin 1 ◽

Full Thickness ◽

Mice Model ◽

Small Peptides ◽

Newborn Mice ◽

Proliferative Effect ◽

Inflammatory Phase

Prokineticins are highly conserved small peptides family expressed in all vertebrates, which contain a wide spectrum of functions. In this study, a prokineticin homolog (Bv8-AJ) isolated from the venom of frog Amolops jingdongensis was fully characterized. Bv8-AJ accelerated full-thickness wounds healing of mice model by promoting the initiation and the termination of inflammatory phase. Moreover, Bv8-AJ exerted strong proliferative effect on fibroblasts and keratinocytes isolated from newborn mice by activating interleukin (IL)-1 production. Our findings indicate that Bv8 is a potent wound healing regulator and may reveal the mechanism of rapid wound-healing in amphibian skins.

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