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RNA exosome

Kei-Hoi Cheung, Shivakumar Keerthikumar, Paola Roncaglia, Sai Lakshmi Subramanian, Matthew E Roth, Monisha Samuel, Sushma Anand, Lahiru Gangoda, Stephen Gould, Roger Alexander, David Galas, Mark B Gerstein, Andrew F Hill, Robert R Kitchen, Jan Lötvall, Tushar Patel, Dena C Procaccini, Peter Quesenberry, Joel Rozowsky, Robert L Raffai, Aleksandra Shypitsyna, Andrew I Su, Clotilde Théry, Kasey Vickers, Marca H M Wauben, Suresh Mathivanan, Aleksandar Milosavljevic, Louise C Laurent
BACKGROUND: To address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research. METHODS: By following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO...
April 12, 2016: Journal of Biomedical Semantics
Yuan Ren, Nan Ji, Xixiong Kang, Renzhi Wang, Wenbin Ma, Zhenjun Hu, Xingfeng Liu, Yajie Wang
Glioblastoma is a highly vascularized brain tumor that causes high mortality. Kininogen-1 (KNG1) has demonstrated both tumor suppressor and antiangiogenesis properties in gliobastoma cells. We analyzed the microarray and proteomic profiles of tumor tissues from glioblastoma patients (N = 180), and identified potential RNA regulators of the KNG1. Validation experiments in U87 glioblastoma cells showed that the regulation of KNG1 by CTU1, KIAA1274, and RAX was mediated by miR-138. The siRNA-mediated knockdown of CTU1, KIAA1274, or RAX in U87 cells and immortalized human endothelial cells (iHECs) significantly reduced KNG1 expression (P < 0...
October 14, 2016: Oncotarget
Kristin M Klohonatz, Ashley D Cameron, Joanna R Hergenreder, Juliano C da Silveira, Aeriel D Belk, D N R Veeramachaneni, Gerrit J Bouma, Jason E Bruemmer
During early pregnancy the conceptus and mare communicate to establish pregnancy. Cell-secreted vesicles (e.g. exosomes) have been reported in serum. Exosomes contain bioactive materials, such as miRNA, that can mediate cell responses. We hypothesized that (i) exosomes are present in mare circulation and quantity varies with pregnancy status, (ii) exosomes contain miRNAs unique to pregnancy status, and (iii) miRNAs target pathways in endometrium based upon pregnancy status of the mare. First, serum samples were obtained from mares in a crossover design, with each mare providing samples from a pregnant and non-mated control cycle (n = 3/sample day) on Days 12, 14, 16, and 18 post-ovulation...
October 19, 2016: Biology of Reproduction
Xiang Yu, Matthew R Willmann, Stephen J Anderson, Brian D Gregory
RNA turnover is necessary for controlling proper mRNA levels post-transcriptionally. In general, RNA degradation is via exoribonucleases that degrade RNA either from the 5' end to the 3' end, such as XRN4, or in the opposite direction by the multi-subunit exosome complex. Here, we use genome-wide mapping of uncapped and cleaved transcripts to reveal the global landscape of co-translational mRNA decay in the Arabidopsis thaliana transcriptome. We found that this process leaves a clear three nucleotide periodicity in open reading frames...
October 7, 2016: Plant Cell
Jason Zhu, John H Strickler
"Liquid biopsies" are blood based assays used to detect and analyze circulating tumor products, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating messenger RNA (mRNA), circulating microRNA (miRNA), circulating exosomes, and tumor educated platelets (TEP). For patients with gastrointestinal (GI) malignancies, blood based biopsies may offer several advantages. First, tumor tissue samples are often challenging to procure, and when obtainable, are often insufficient for genomic profiling...
October 2016: Journal of Gastrointestinal Oncology
Igor Slivac, David Guay, Mathias Mangion, Juliette Champeil, Bruno Gaillet
Delivery of nucleic acid-based molecules in human cells is a highly studied approach for the treatment of several disorders including monogenic diseases and cancers. Non-viral vectors for DNA and RNA transfer, although in general less efficient than virus-based systems, are particularly well adapted mostly due to the absence of biosafety concerns. Non-viral methods could be classified in two main groups: physical and vector-assisted delivery systems. Both groups comprise several different methods, none of them universally applicable...
October 14, 2016: Expert Opinion on Biological Therapy
Marzia Del Re, Elisa Biasco, Stefania Crucitta, Lisa Derosa, Eleonora Rofi, Cinzia Orlandini, Mario Miccoli, Luca Galli, Alfredo Falcone, Guido W Jenster, Ron H van Schaik, Romano Danesi
BACKGROUND: The androgen receptor splice variant 7 (AR-V7) is associated with resistance to hormonal therapy in castration-resistant prostate cancer (CRPC). Due to limitations of the methods available for AR-V7 analysis, the identification of a reliable detection method may facilitate the use of this biomarker in clinical practice. OBJECTIVE: To confirm AR-V7 as a predictor of resistance to hormonal therapy and develop a new approach to assess AR-V7 by highly sensitive digital droplet polymerase chain reaction (ddPCR) in plasma-derived exosomal RNA...
August 26, 2016: European Urology
Laura Santangelo, Giorgio Giurato, Carla Cicchini, Claudia Montaldo, Carmine Mancone, Roberta Tarallo, Cecilia Battistelli, Tonino Alonzi, Alessandro Weisz, Marco Tripodi
Despite clear evidence that exosomal microRNAs (miRNAs) are able to modulate the cellular microenvironment and that exosomal RNA cargo selection is deregulated in pathological conditions, the mechanisms controlling specific RNA sorting into extracellular vesicles are still poorly understood. Here, we identified the RNA binding protein SYNCRIP (synaptotagmin-binding cytoplasmic RNA-interacting protein; also known as hnRNP-Q or NSAP1) as a component of the hepatocyte exosomal miRNA sorting machinery. SYNCRIP knockdown impairs sorting of miRNAs in exosomes...
October 11, 2016: Cell Reports
Thomas Westergard, Brigid K Jensen, Xinmei Wen, Jingli Cai, Elizabeth Kropf, Lorraine Iacovitti, Piera Pasinelli, Davide Trotti
Aberrant hexanucleotide repeat expansions in C9orf72 are the most common genetic change underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). RNA transcripts containing these expansions undergo repeat-associated non-ATG translation (RAN-T) to form five dipeptide repeat proteins (DPRs). DPRs are found as aggregates throughout the CNS of C9orf72-ALS/FTD patients, and some cause degeneration when expressed in vitro in neuronal cultures and in vivo in animal models. The spread of characteristic disease-related proteins drives the progression of pathology in many neurodegenerative diseases...
October 11, 2016: Cell Reports
Yusuke Yoshioka, Takahiro Ochiya
Exosomes are membrane vesicles approximately 100 nm in diameter, present in a wide range of body fluids, including blood, cerebrospinal fluid, urine and saliva. Exosomes reflect the physiological state of their cells of origin and cancer cell-derived exosomes carry pathogenic components, such as proteins, messenger RNA (mRNA), microRNA (miRNA), and DNA. Thus, exosomes in body fluids provide a rich source of potential biomarkers. However, the use of exosomes as biomarkers to improve patient care has been limited by their small size and the extensive sample preparation required for their isolation and measurement...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Shota Suzuki, Yota Murakami, Shinya Takahata
Epigenetic marks determine cell fate via numerous reader proteins. H3K36 methylation is a common epigenetic mark that is thought to be associated with the activities of the RNA polymerase 2 C-terminal domain. We discuss a novel silencing mechanism regulated by Set2-dependent H3K36 methylation that involves exosome-dependent RNA processing.
October 10, 2016: Transcription
Atsuko Miki, Josephine Galipon, Satoshi Sawai, Toshifumi Inada, Kunihiro Ohta
Antisense RNA has emerged as a crucial regulator of opposite-strand protein-coding genes in the long noncoding RNA (lncRNA) category, but little is known about their dynamics and decay process in the context of a stress response. Antisense transcripts from the fission yeast fbp1 locus (fbp1-as) are expressed in glucose-rich conditions and anticorrelated with transcription of metabolic stress-induced lncRNA (mlonRNA) and mRNA on the sense strand during glucose starvation. Here, we investigate the localization and decay of antisense RNAs at fbp1 and other loci, and propose a model to explain the rapid switch between antisense and sense mlonRNA/mRNA transcription triggered by glucose starvation...
October 10, 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Zhen Qu, Junhua Wu, Junyi Wu, Dongjun Luo, Chunping Jiang, Yitao Ding
BACKGROUND: Exosomes are carriers of intercellular information and regulate the tumor microenvironment. They play an important role in drug resistance by transporting RNA molecules and proteins. However, their effects on sorafenib resistance in hepatocellular carcinoma (HCC) are not completely understood. METHODS: Exosomes were isolated from two invasive hepatoma cell lines (MHCC-97 L and MHCC-97H), and their roles in regulating sorafenib resistance in liver cancer cells as well as the underlying molecular mechanisms were determined...
September 30, 2016: Journal of Experimental & Clinical Cancer Research: CR
Paul A Rowley, Brandon Ho, Sarah Bushong, Arlen Johnson, Sara L Sawyer
In eukaryotes, the degradation of cellular mRNAs is accomplished by Xrn1 and the cytoplasmic exosome. Because viral RNAs often lack canonical caps or poly-A tails, they can also be vulnerable to degradation by these host exonucleases. Yeast lack sophisticated mechanisms of innate and adaptive immunity, but do use RNA degradation as an antiviral defense mechanism. One model is that the RNA of yeast viruses is subject to degradation simply as a side effect of the intrinsic exonuclease activity of proteins involved in RNA metabolism...
October 2016: PLoS Pathogens
Abderrahim Benmoussa, Chan Ho C Lee, Benoit Laffont, Patricia Savard, Jonathan Laugier, Eric Boilard, Caroline Gilbert, Ismail Fliss, Patrick Provost
BACKGROUND: MicroRNAs are small, gene-regulatory noncoding RNA species present in large amounts in milk, where they seem to be protected against degradative conditions, presumably because of their association with exosomes. OBJECTIVE: We monitored the relative stability of commercial dairy cow milk microRNAs during digestion and examined their associations with extracellular vesicles (EVs). METHODS: We used a computer-controlled, in vitro, gastrointestinal model TNO intestinal model-1 (TIM-1) and analyzed, by quantitative polymerase chain reaction, the concentration of 2 microRNAs within gastrointestinal tract compartments at different points in time...
October 5, 2016: Journal of Nutrition
Yao Zhao, Kaiyong Chen, Haining Li, Huiyi Wu
PURPOSE: Urinary exosome is an ideal noninvasive, low-cost source of kidney diseases biomarkers. However, many factors effect the isolation of urine-derived exosome. The effect of pH on the yield of exosome isolation under different pH was explored. METHODS: The pH was adjusted for 4, 5, 6, 7 and 8 with hydrochloric acid and sodium hydroxide solution. All samples were incubated for 30 min before differential ultracentrifugation. Exosome-associated protein markers TSG101, ALIX and total concentration of RNA were evaluated by Western-blotting and micro-amount ultraviolet spectrophotometer, respectively...
September 27, 2016: International Urology and Nephrology
Marco Giallombardo, Pablo Reclusa, Anna Valentino, Rafael Sirera, Patrick Pauwels, Christian Rolfo
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
Camelia Quek, Andrew F Hill
Extracellular vesicles, including exosomes, are small membranous vesicles released from many biotypes, contributing to the disease progression and spreading. These extracellular vesicles provide an important mode of cell-to-cell communication by delivering proteins, lipids and RNA to target cells. Exosomes are found associated with neurodegenerative diseases, which are characterised by progressive degeneration of neurons and often associated with misfolded protein. The common diseases include Parkinson's disease (PD), Alzheimer's diseases (AD), amyotrophic lateral sclerosis (ALS), and the prion diseases...
September 19, 2016: Biochemical and Biophysical Research Communications
Jing Li, Xiulan Chen, Jiao Yi, Yuchen Liu, Dameng Li, Jifeng Wang, Dongxia Hou, Xiaohong Jiang, Junfeng Zhang, Jin Wang, Ke Zen, Fuquan Yang, Chen-Yu Zhang, Yujing Zhang
Cell-derived exosomes are leading candidates for in vivo drug delivery carriers. In particular, exosomes derived from 293T cells are used most frequently, although exosome dosing has varied greatly among studies. Considering their biological origin, it is crucial to characterize the molecular composition of exosomes if large doses are to be administered in clinical settings. In this study, we present the first comprehensive analysis of the protein, messenger RNA and microRNA profiles of 293T cell-derived exosomes; then, we characterized these data using Gene Ontology annotation and Kyoto Encyclopedia for Genes and Genomes pathway analysis...
2016: PloS One
Ting Chen, Mei-Ying Xie, Jia-Jie Sun, Rui-Song Ye, Xiao Cheng, Rui-Ping Sun, Li-Min Wei, Meng Li, De-Lin Lin, Qing-Yan Jiang, Qian-Yun Xi, Yong-Liang Zhang
Milk-derived exosomes were identified as a novel mechanism of mother-to-child transmission of regulatory molecules, but their functions in intestinal tissues of neonates are not well-studied. Here, we characterized potential roles of porcine milk-derived exosomes in the intestinal tract. In vitro, treatment with milk-derived exosomes (27 ± 3 ng and 55 ± 5 ng total RNA) significantly promoted IPEC-J2 cell proliferation by MTT, CCK8, EdU fluorescence and EdU flow cytometry assays. The qRT-PCR and Western blot analyses indicated milk-derived exosomes (0...
2016: Scientific Reports
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