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RNA epigenetic

Yong-Eun Kim, Chungoo Park, Kyoon Eon Kim, Kee K Kim
Alternative splicing is an essential process in eukaryotes, as it increases the complexity of gene expression by generating multiple proteins from a single pre-mRNA. However, information on the regulatory mechanisms for alternative splicing is lacking, because splicing occurs over a short period via the transient interactions of proteins within functional complexes of the spliceosome. Here, we investigated in detail the molecular mechanisms connecting alternative splicing with epigenetic mechanisms. We identified interactions between histone proteins and splicing factors such as Rbfox2, Rbfox3, and splicing factor proline and glutamine rich protein (SFPQ) by in vivo crosslinking and immunoprecipitation...
March 15, 2018: Biochemical and Biophysical Research Communications
David G Ashbrook, Benjamin Hing, Lindsay T Michalovicz, Kimberly A Kelly, Julie V Miller, Wilfred C de Vega, Diane B Miller, Gordon Broderick, James P O'Callaghan, Patrick O McGowan
BACKGROUND: Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and neuroimmune and neuroinflammatory components. An estimated 25-32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the neuroimmune system...
March 17, 2018: Journal of Neuroinflammation
Ali Movahedi, Jiaxin Zhang, Weibo Sun, Kourosh Mohammadi, Amir Almasi Zadeh Yaghuti, Hui Wei, Xiaolong Wu, Tongming Yin, Qiang Zhuge
Epigenetic modification by DNA methylation is necessary for all cellular processes, including genetic expression events, DNA repair, genomic imprinting and regulation of tissue development. It occurs almost exclusively at the C5 position of symmetric CpG and asymmetric CpHpG and CpHpH sites in genomic DNA. The RNA-directed DNA methylation (RDM1) gene is crucial for heterochromatin and DNA methylation. We overexpressed PtRDM1 gene from Populus trichocarpa to amplify transcripts of orthologous RDM1 in 'Nanlin895' (P...
March 10, 2018: Plant Physiology and Biochemistry: PPB
Yue Guo, Renyi Wu, John M Gaspar, Davit Sargsyan, Zheng-Yuan Su, Chengyue Zhang, Linbo Gao, David Cheng, Wenji Li, Chao Wang, Ran Yin, Mingzhu Fang, Michael P Verzi, Ronald P Hart, Ah-Ng Kong
Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in AOM-DSS mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anti-cancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed...
March 14, 2018: Carcinogenesis
Zhiyi Qin, Peter Stoilov, Xuegong Zhang, Yi Xing
Alternative first exons diversify the transcriptomes of eukaryotes by producing variants of the 5' Untranslated Regions (5'UTRs) and N-terminal coding sequences. Accurate transcriptome-wide detection of alternative first exons typically requires specialized experimental approaches that are designed to identify the 5' ends of transcripts. We developed a computational pipeline SEASTAR that identifies first exons from RNA-seq data alone then quantifies and compares alternative first exon usage across multiple biological conditions...
March 13, 2018: Nucleic Acids Research
Robert John Aitken
This article is a personal perspective on male infertility, a condition that is not only extremely prevalent but also a major reason for couples to resort to assisted reproductive technology. The introduction of intra-cytoplasmic sperm injection (ICSI) as a form of facilitated fertilization had a revolutionary impact on our capacity to treat cases of male infertility associated with severely-compromised semen quality. However, the widespread use of this technique is also thought to pose risks in terms of the incidence of miscarriage, the health and wellbeing of the offspring and perpetuation of the infertile phenotype into future generations...
March 13, 2018: Molecular Human Reproduction
Ximena Corso-Díaz, Catherine Jaeger, Vijender Chaitankar, Anand Swaroop
Complex biological processes, such as organogenesis and homeostasis, are stringently regulated by genetic programs that are fine-tuned by epigenetic factors to establish cell fates and/or to respond to the microenvironment. Gene regulatory networks that guide cell differentiation and function are modulated and stabilized by modifications to DNA, RNA and proteins. In this review, we focus on two key epigenetic changes - DNA methylation and histone modifications - and discuss their contribution to retinal development, aging and disease, especially in the context of age-related macular degeneration (AMD) and diabetic retinopathy...
March 12, 2018: Progress in Retinal and Eye Research
Tingchao Mao, Chengquan Han, Ruizhi Deng, Biao Wei, Peng Meng, Yan Luo, Yong Zhang
Epigenetic modifications extensively occur in mammalian embryonic development and cell differentiation process. They play an essential role in the reprogramming of nuclei during somatic cell nuclear transfer (SCNT) and subsequent in vitro embryonic development. Recently, SCNT embryos have been verified to contain a subnormal level of histone H3K4 dimethylation (H3K4me2) in contrast to in vitro fertilized embryos. This finding suggested that increasing H3K4me2 levels may ameliorate the aberrant development of cloned embryos...
March 15, 2018: Systems Biology in Reproductive Medicine
Weizhi Yu, Hong Xu, Ying Xue, Dong An, Huairui Li, Wei Chen, Deqin Yu, Yiping Sun, Jianmei Ma, Yiyuan Tang, Zhaoyang Xiao, Shengming Yin
Introduction: Social isolation enhances the aggressive behavior of animals, but the detailed mechanism remains unclear. Epigenetic studies have suggested that Htr2c RNA editing is closely related to aggressive behavior. This study aims to obtain a fundamental understanding of how social isolation impacts adenosine deaminase acting on RNA 1 (ADAR1, RNA editing enzyme) and Htr2c RNA editing, leading to aggressive behavior, and explore the effective solutions for the recovery of this behavior...
March 2018: Brain and Behavior
Guangyong Zheng, Tao Huang
In post-genomic era, an important task is to explore the function of individual biological molecules (i.e., gene, noncoding RNA, protein, metabolite) and their organization in living cells. For this end, gene regulatory networks (GRNs) are constructed to show relationship between biological molecules, in which the vertices of network denote biological molecules and the edges of network present connection between nodes (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). Biologists can understand not only the function of biological molecules but also the organization of components of living cells through interpreting the GRNs, since a gene regulatory network is a comprehensively physiological map of living cells and reflects influence of genetic and epigenetic factors (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003)...
2018: Methods in Molecular Biology
Kun Qian, Hao Hu, Hui Xu, Y George Zheng
Protein arginine methyltransferases (PRMTs) are crucial epigenetic regulators in eukaryotic organisms that serve as histone writers for chromatin remodeling. PRMTs also methylate a variety of non-histone protein substrates to modulate their function and activity. The development of potent PRMT inhibitors has become an emerging and imperative research area in the drug discovery field to provide novel therapeutic agents for treating diseases and as tools to investigate the biological functions of PRMTs. PRMT1 is the major type I enzyme that catalyzes the formation of asymmetric dimethyl arginine, and PRMT1 plays important regulatory roles in signal transduction, transcriptional activation, RNA splicing, and DNA repair...
2018: Signal Transduction and Targeted Therapy
Marie E Gaine, Snehajyoti Chatterjee, Ted Abel
Sleep deprivation disrupts the lives of millions of people every day and has a profound impact on the molecular biology of the brain. These effects begin as changes within a neuron, at the DNA and RNA level, and result in alterations in neuronal plasticity and dysregulation of many cognitive functions including learning and memory. The epigenome plays a critical role in regulating gene expression in the context of memory storage. In this review article, we begin by describing the effects of epigenetic alterations on the regulation of gene expression, focusing on the most common epigenetic mechanisms: (i) DNA methylation; (ii) histone modifications; and (iii) non-coding RNAs...
2018: Frontiers in Neural Circuits
Ning Wang, Yanan Zhu, Min Xie, Lintao Wang, Feiyan Jin, Yihui Li, Qingxin Yuan, Wei De
BACKGROUND/AIMS: The main pathogenic mechanism of diabetes is a decrease in the number of islet beta cells or a decline in their function. Recent studies have shown that pancreatic long noncoding RNAs (lncRNAs) have a high degree of tissue specificity and may be involved in the maintenance of islet cells function and the development of diabetes. The aim of this study was to investigate the molecular regulatory mechanism of mouse maternal expressed gene 3 (Meg3) in insulin biosynthesis in pancreatic islets...
March 6, 2018: Cellular Physiology and Biochemistry
Dandan Yang, Jing Qiao, Guiying Wang, Yuanyuan Lan, Guoping Li, Xudong Guo, Jiajie Xi, Dan Ye, Songcheng Zhu, Wen Chen, Wenwen Jia, Ye Leng, Xiaoping Wan, Jiuhong Kang
Previous studies have revealed the critical roles of N6-methyladenosine (m6A) modification of mRNA in embryonic stem cells (ESCs), but the biological function of m6A in large intergenic noncoding RNA (lincRNA) is unknown. Here, we showed that the internal m6A modification of linc1281 mediates a competing endogenous RNA (ceRNA) model to regulate mouse ESC (mESC) differentiation. We demonstrated that loss of linc1281 compromises mESC differentiation and that m6A is highly enriched within linc1281 transcripts...
February 26, 2018: Nucleic Acids Research
Rachel L Clifford, Nick Fishbane, Jamie Patel, Julia L MacIsaac, Lisa M McEwen, Andrew J Fisher, Corry-Anke Brandsma, Parameswaran Nair, Michael S Kobor, Tillie-Louise Hackett, Alan J Knox
Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease of the lungs that is currently the fourth leading cause of death worldwide. Genetic factors account for only a small amount of COPD risk, but epigenetic mechanisms, including DNA methylation, have the potential to mediate the interactions between an individual's genetics and environmental exposure. DNA methylation is highly cell type-specific, and individual cell type studies of DNA methylation in COPD are sparse...
2018: Clinical Epigenetics
William Beckman, Ilona M Vuist, Hermannus Kempe, Pernette J Verschure
Single-molecule RNA fluorescent in situ hybridization (smRNA FISH) allows for the visualization, localization, and quantification of RNA transcripts within individual cells and tissues using custom-designed fluorescently labeled oligonucleotide probes. Here we describe a protocol for the preparation, imaging, and analysis of a smRNA FISH experiment that can be applied to any RNA of choice. We also provide insights as to how this powerful tool can be used to study epigenetic regulation, for example, following the epigenetic editing of genes...
2018: Methods in Molecular Biology
Afraa Mamoori, Vinod Gopalan, Alfred K-Y Lam
BACKGROUND: There is emerging data suggest that the non-coding RNA (microRNA 193a or miR-193a) plays key roles in different types of cancers. OBJECTIVE: This review aims to investigate the functional significance of miR-193a in different cancers according to the information of literature. METHOD: All the literature concerning miR-193a in cancer in PubMed are analysed. RESULTS: Several studies proved the association of miR-193a expression patterns with cancer's stages, grades, response to the chemotherapy and even patient survival...
March 7, 2018: Current Cancer Drug Targets
Christian L Lino Cardenas, Chase W Kessinger, Yisha Cheng, Carolyn MacDonald, Thomas MacGillivray, Brian Ghoshhajra, Luai Huleihel, Saifar Nuri, Ashish S Yeri, Farouc A Jaffer, Naftali Kaminski, Patrick Ellinor, Neal L Weintraub, Rajeev Malhotra, Eric M Isselbacher, Mark E Lindsay
Thoracic aortic aneurysm (TAA) has been associated with mutations affecting members of the TGF-β signaling pathway, or components and regulators of the vascular smooth muscle cell (VSMC) actomyosin cytoskeleton. Although both clinical groups present similar phenotypes, the existence of potential common mechanisms of pathogenesis remain obscure. Here we show that mutations affecting TGF-β signaling and VSMC cytoskeleton both lead to the formation of a ternary complex comprising the histone deacetylase HDAC9, the chromatin-remodeling enzyme BRG1, and the long noncoding RNA MALAT1...
March 8, 2018: Nature Communications
Lauriane Simon, Fernando A Rabanal, Tristan Dubos, Cecilia Oliver, Damien Lauber, Axel Poulet, Alexander Vogt, Ariane Mandlbauer, Samuel Le Goff, Andreas Sommer, Hervé Duborjal, Christophe Tatout, Aline V Probst
Organized in tandem repeat arrays in most eukaryotes and transcribed by RNA polymerase III, expression of 5S rRNA genes is under epigenetic control. To unveil mechanisms of transcriptional regulation, we obtained here in depth sequence information on 5S rRNA genes from the Arabidopsis thaliana genome and identified differential enrichment in epigenetic marks between the three 5S rDNA loci situated on chromosomes 3, 4 and 5. We reveal the chromosome 5 locus as the major source of an atypical, long 5S rRNA transcript characteristic of an open chromatin structure...
March 6, 2018: Nucleic Acids Research
Alexis H Bennett, Marie-Francoise O'Donohue, Stacey R Gundry, Aye T Chan, Jeffrey Widrick, Isabelle Draper, Anirban Chakraborty, Yi Zhou, Leonard I Zon, Pierre-Emmanuel Gleizes, Alan H Beggs, Vandana A Gupta
Gene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration...
March 2018: PLoS Genetics
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