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

2017 ◽  
Vol 114 (50) ◽  
pp. 13296-13301 ◽  
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.

scholarly journals Mitochondrial Glucocorticoid Receptors and Their Actions

2021 ◽  
Vol 22 (11) ◽  
pp. 6054
Author(s):  
Ioanna Kokkinopoulou ◽  
Paraskevi Moutsatsou
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptors ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Ros Generation ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Energy Metabolism ◽  
Bcl2 Family ◽  
Cellular Processes ◽  
Almost All

Mitochondria are membrane organelles present in almost all eukaryotic cells. In addition to their well-known role in energy production, mitochondria regulate central cellular processes, including calcium homeostasis, Reactive Oxygen Species (ROS) generation, cell death, thermogenesis, and biosynthesis of lipids, nucleic acids, and steroid hormones. Glucocorticoids (GCs) regulate the mitochondrially encoded oxidative phosphorylation gene expression and mitochondrial energy metabolism. The identification of Glucocorticoid Response Elements (GREs) in mitochondrial sequences and the detection of Glucocorticoid Receptor (GR) in mitochondria of different cell types gave support to hypothesis that mitochondrial GR directly regulates mitochondrial gene expression. Numerous studies have revealed changes in mitochondrial gene expression alongside with GR import/export in mitochondria, confirming the direct effects of GCs on mitochondrial genome. Further evidence has made clear that mitochondrial GR is involved in mitochondrial function and apoptosis-mediated processes, through interacting or altering the distribution of Bcl2 family members. Even though its exact translocation mechanisms remain unknown, data have shown that GR chaperones (Hsp70/90, Bag-1, FKBP51), the anti-apoptotic protein Bcl-2, the HDAC6- mediated deacetylation and the outer mitochondrial translocation complexes (Tom complexes) co-ordinate GR mitochondrial trafficking. A role of mitochondrial GR in stress and depression as well as in lung and hepatic inflammation has also been demonstrated.

scholarly journals Mutational analysis of apolipoprotein B mRNA editing enzyme (APOBEC1): structure–function relationships of RNA editing and dimerization

1999 ◽  
Vol 40 (4) ◽  
pp. 623-635 ◽  
Author(s):  
Ba-Bie Teng ◽  
Scott Ochsner ◽  
Qian Zhang ◽  
Kizhake V. Soman ◽  
Paul P. Lau ◽  
...  
Keyword(s):  
Structure Function ◽  
Rna Editing ◽  
Apolipoprotein B ◽  
Mutational Analysis ◽  
Mrna Editing ◽  
Editing Enzyme

scholarly journals Competing Endogenous RNAs in Cervical Carcinogenesis: A New Layer of Complexity

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 991
Author(s):  
Fernanda Costa Brandão Berti ◽  
Sara Cristina Lobo-Alves ◽  
Camila de Freitas Oliveira-Toré ◽  
Amanda Salviano-Silva ◽  
Karen Brajão de Oliveira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Cervical Carcinogenesis ◽  
Molecular Changes ◽  
Cellular Processes ◽  
Target Mrnas ◽  
Competing Endogenous Rnas ◽  
Cervical Cells ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) regulate gene expression by binding to complementary sequences within target mRNAs. Apart from working ‘solo’, miRNAs may interact in important molecular networks such as competing endogenous RNA (ceRNA) axes. By competing for a limited pool of miRNAs, transcripts such as long noncoding RNAs (lncRNAs) and mRNAs can regulate each other, fine-tuning gene expression. Several ceRNA networks led by different lncRNAs—described here as lncRNA-mediated ceRNAs—seem to play essential roles in cervical cancer (CC). By conducting an extensive search, we summarized networks involved in CC, highlighting the major impacts of such dynamic molecular changes over multiple cellular processes. Through the sponging of distinct miRNAs, some lncRNAs as HOTAIR, MALAT1, NEAT1, OIP5-AS1, and XIST trigger crucial molecular changes, ultimately increasing cell proliferation, migration, invasion, and inhibiting apoptosis. Likewise, several lncRNAs seem to be a sponge for important tumor-suppressive miRNAs (as miR-140-5p, miR-143-3p, miR-148a-3p, and miR-206), impairing such molecules from exerting a negative post-transcriptional regulation over target mRNAs. Curiously, some of the involved mRNAs code for important proteins such as PTEN, ROCK1, and MAPK1, known to modulate cell growth, proliferation, apoptosis, and adhesion in CC. Overall, we highlight important lncRNA-mediated functional interactions occurring in cervical cells and their closely related impact on cervical carcinogenesis.

scholarly journals Nuclear genetic regulation of the human mitochondrial transcriptome

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Aminah T Ali ◽  
Lena Boehme ◽  
Guillermo Carbajosa ◽  
Vlad C Seitan ◽  
Kerrin S Small ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Genome ◽  
Complex Disease ◽  
Genetic Regulation ◽  
Cell Types ◽  
Tissue Cell ◽  
Cellular Processes ◽  
Genetic Mechanisms ◽  
Cell Type Specific ◽  
Nuclear Loci

Mitochondria play important roles in cellular processes and disease, yet little is known about how the transcriptional regime of the mitochondrial genome varies across individuals and tissues. By analyzing >11,000 RNA-sequencing libraries across 36 tissue/cell types, we find considerable variation in mitochondrial-encoded gene expression along the mitochondrial transcriptome, across tissues and between individuals, highlighting the importance of cell-type specific and post-transcriptional processes in shaping mitochondrial-encoded RNA levels. Using whole-genome genetic data we identify 64 nuclear loci associated with expression levels of 14 genes encoded in the mitochondrial genome, including missense variants within genes involved in mitochondrial function (TBRG4, MTPAP and LONP1), implicating genetic mechanisms that act in trans across the two genomes. We replicate ~21% of associations with independent tissue-matched datasets and find genetic variants linked to these nuclear loci that are associated with cardio-metabolic phenotypes and Vitiligo, supporting a potential role for variable mitochondrial-encoded gene expression in complex disease.

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

2021 ◽  
Vol 5 (3) ◽  
pp. e202101191
Author(s):  
Xinfeng Guo ◽  
Silvia Liu ◽  
Rose Yan ◽  
Vy Nguyen ◽  
Mazen Zenati ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Rna Editing ◽  
Sequencing Analysis ◽  
Newborn Mice ◽  
Interferon Stimulated Genes ◽  
Cell Functions ◽  
Multiple Organs ◽  
Elevated Expression ◽  
Editing Enzyme

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.

Septins in the glial cells of the nervous system

2014 ◽  
Vol 395 (2) ◽  
pp. 143-149 ◽  
Author(s):  
Julia Patzig ◽  
Michelle S. Dworschak ◽  
Ann-Kristin Martens ◽  
Hauke B. Werner
Keyword(s):  
Nervous System ◽  
Schwann Cells ◽  
Glial Cells ◽  
Current Knowledge ◽  
Cell Types ◽  
Higher Order ◽  
Neuralgic Amyotrophy ◽  
Cellular Processes ◽  
Functional Relevance ◽  
Order Structures

Abstract The capacity of cytoskeletal septins to mediate diverse cellular processes is related to their ability to assemble as distinct heterooligomers and higher order structures. However, in many cell types the functional relevance of septins is not well understood. This minireview provides a brief overview of our current knowledge about septins in the non-neuronal cells of the vertebrate nervous system, collectively termed ‘glial cells’, i.e., astrocytes, microglia, oligodendrocytes, and Schwann cells. The dysregulation of septins observed in various models of myelin pathology is discussed with respect to implications for hereditary neuralgic amyotrophy (HNA) caused by mutations of the human SEPT9-gene.

scholarly journals Co-expression analysis reveals interpretable gene modules controlled by trans-acting genetic variants

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Liis Kolberg ◽  
Nurlan Kerimov ◽  
Hedi Peterson ◽  
Kaur Alasoo
Keyword(s):  
Gene Expression ◽  
Multiple Testing ◽  
Disease Onset ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Cell Types ◽  
Functional Enrichment ◽  
Eqtl Analysis ◽  
Cellular Processes ◽  
Causal Processes

Understanding the causal processes that contribute to disease onset and progression is essential for developing novel therapies. Although trans-acting expression quantitative trait loci (trans-eQTLs) can directly reveal cellular processes modulated by disease variants, detecting trans-eQTLs remains challenging due to their small effect sizes. Here, we analysed gene expression and genotype data from six blood cell types from 226 to 710 individuals. We used co-expression modules inferred from gene expression data with five methods as traits in trans-eQTL analysis to limit multiple testing and improve interpretability. In addition to replicating three established associations, we discovered a novel trans-eQTL near SLC39A8 regulating a module of metallothionein genes in LPS-stimulated monocytes. Interestingly, this effect was mediated by a transient cis-eQTL present only in early LPS response and lost before the trans effect appeared. Our analyses highlight how co-expression combined with functional enrichment analysis improves the identification and prioritisation of trans-eQTLs when applied to emerging cell-type-specific datasets.

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