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exosome RNA

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https://www.readbyqxmd.com/read/29773668/plants-send-small-rnas-in-extracellular-vesicles-to-fungal-pathogen-to-silence-virulence-genes
#1
Qiang Cai, Lulu Qiao, Ming Wang, Baoye He, Feng-Mao Lin, Jared Palmquist, Hsien-Da Huang, Hailing Jin
Some pathogens and pests deliver small RNAs (sRNAs) into host cells to suppress host immunity. Conversely, hosts also transfer sRNAs into pathogens and pests to inhibit their virulence. Although sRNA trafficking has been observed in a wide variety of interactions, how sRNAs are transferred, especially from hosts to pathogens/pests, is still unknown. Here we show that host Arabidopsis cells secrete exosome-like extracellular vesicles to deliver sRNAs into fungal pathogen Botrytis cinerea These sRNA-containing vesicles accumulate at the infection sites and are taken up by the fungal cells...
May 17, 2018: Science
https://www.readbyqxmd.com/read/29769566/antiretroviral-drugs-alter-the-content-of-extracellular-vesicles-from-hiv-1-infected-cells
#2
Catherine DeMarino, Michelle L Pleet, Maria Cowen, Robert A Barclay, Yao Akpamagbo, James Erickson, Nicaise Ndembe, Manhattan Charurat, Jibreel Jumare, Sunday Bwala, Peter Alabi, Max Hogan, Archana Gupta, Nicole Noren Hooten, Michele K Evans, Benjamin Lepene, Weidong Zhou, Massimo Caputi, Fabio Romerio, Walter Royal, Nazira El-Hage, Lance A Liotta, Fatah Kashanchi
To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769437/exosome-delivered-micrornas-promote-ifn-%C3%AE-secretion-by-human-plasmacytoid-dcs-via-tlr7
#3
Valentina Salvi, Veronica Gianello, Sara Busatto, Paolo Bergese, Laura Andreoli, Ugo D'Oro, Alessandra Zingoni, Angela Tincani, Silvano Sozzani, Daniela Bosisio
The excessive production of type I IFNs is a hallmark and a main pathogenic mechanism of many autoimmune diseases, including systemic lupus erythematosus (SLE). In these pathologies, the sustained secretion of type I IFNs is dependent on the improper activation of plasmacytoid DCs (pDCs) by self-nucleic acids. However, the nature and origin of pDC-activating self-nucleic acids is still incompletely characterized. Here, we report that exosomes isolated from the plasma of SLE patients can activate the secretion of IFN-α by human blood pDCs in vitro...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29768216/the-rna-exosome-adaptor-zfc3h1-functionally-competes-with-nuclear-export-activity-to-retain-target-transcripts
#4
Toomas Silla, Evdoxia Karadoulama, Dawid Mąkosa, Michal Lubas, Torben Heick Jensen
Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA+ ) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with "pA-tail exosome targeting (PAXT) connection" components MTR4, ZFC3H1, and PABPN1 but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29760697/hookworm-secreted-extracellular-vesicles-interact-with-host-cells-and-prevent-inducible-colitis-in-mice
#5
Ramon M Eichenberger, Stephanie Ryan, Linda Jones, Geraldine Buitrago, Ramona Polster, Marcela Montes de Oca, Jennifer Zuvelek, Paul R Giacomin, Lindsay A Dent, Christian R Engwerda, Matthew A Field, Javier Sotillo, Alex Loukas
Gastrointestinal (GI) parasites, hookworms in particular, have evolved to cause minimal harm to their hosts, allowing them to establish chronic infections. This is mediated by creating an immunoregulatory environment. Indeed, hookworms are such potent suppressors of inflammation that they have been used in clinical trials to treat inflammatory bowel diseases (IBD) and celiac disease. Since the recent description of helminths (worms) secreting extracellular vesicles (EVs), exosome-like EVs from different helminths have been characterized and their salient roles in parasite-host interactions have been highlighted...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29758258/nuclear-mrna-surveillance-mechanisms-function-and-links-to-human-disease
#6
REVIEW
Pragyan Singh, Upasana Saha, Sunirmal Paira, Biswadip Das
Production of export-competent mRNAs involves transcription and a series of dynamic processing and modification events of pre-messenger RNAs in the nucleus. Mutations in the genes encoding the transcription and mRNP processing machinery and the complexities involved in the biogenesis events lead to the formation of aberrant messages. These faulty transcripts are promptly eliminated by the nuclear RNA exosome and its cofactors to safeguard the cells and organisms from genetic catastrophe. Mutations in the components of the core nuclear exosome and its cofactors lead to the tissue-specific dysfunction of exosomal activities, which are linked to diverse human diseases and disorders...
May 11, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29738525/optimizing-exosomal-rna-isolation-for-rna-seq-analyses-of-archival-sera-specimens
#7
Emily N Prendergast, Marcos Abraão de Souza Fonseca, Felipe Segato Dezem, Jenny Lester, Beth Y Karlan, Houtan Noushmehr, Xianzhi Lin, Kate Lawrenson
Exosomes are endosome-derived membrane vesicles that contain proteins, lipids, and nucleic acids. The exosomal transcriptome mediates intercellular communication, and represents an understudied reservoir of novel biomarkers for human diseases. Next-generation sequencing enables complex quantitative characterization of exosomal RNAs from diverse sources. However, detailed protocols describing exosome purification for preparation of exosomal RNA-sequence (RNA-Seq) libraries are lacking. Here we compared methods for isolation of exosomes and extraction of exosomal RNA from human cell-free serum, as well as strategies for attaining equal representation of samples within pooled RNA-Seq libraries...
2018: PloS One
https://www.readbyqxmd.com/read/29728998/kh-type-splicing-regulatory-protein-is-regulated-by-nuclear-factor-%C3%AE%C2%BAb-signaling-to-mediate-innate-immunity-in-caco-2-cells-infected-by-salmonella-enteritidis
#8
Yuanyang Nie, Mei Cao, Daoyan Wu, Ningzhe Li, Jingshan Peng, Sijun Yi, Xiaofan Yang, Mao Zhang, Guoku Hu, Jian Zhao
Salmonella enteritidis infection occurs in enterogenous diseases, such as gastroenteritis and parenteral focal infection, which often involve inflammation of intestinal epithelial cells. The nuclear factor kappa B (NF-κB) pathway participates in the innate immune response to many gram-negative pathogenic bacteria and initiates inflammation in epithelial cells. KH-type splicing regulatory protein (KSRP) is a multi-domain RNA-binding protein that recruits the exosome-containing mRNA degradation complex to mRNAs coding for inflammatory response factors...
May 4, 2018: Folia Microbiologica
https://www.readbyqxmd.com/read/29727687/variants-in-exosc9-disrupt-the-rna-exosome-and-result-in-cerebellar-atrophy-with-spinal-motor-neuronopathy
#9
David T Burns, Sandra Donkervoort, Juliane S Müller, Ellen Knierim, Diana Bharucha-Goebel, Eissa Ali Faqeih, Stephanie K Bell, Abdullah Y AlFaifi, Dorota Monies, Francisca Millan, Kyle Retterer, Sarah Dyack, Sara MacKay, Susanne Morales-Gonzalez, Michele Giunta, Benjamin Munro, Gavin Hudson, Mena Scavina, Laura Baker, Tara C Massini, Monkol Lek, Ying Hu, Daniel Ezzo, Fowzan S AlKuraya, Peter B Kang, Helen Griffin, A Reghan Foley, Markus Schuelke, Rita Horvath, Carsten G Bönnemann
The exosome is a conserved multi-protein complex that is essential for correct RNA processing. Recessive variants in exosome components EXOSC3, EXOSC8, and RBM7 cause various constellations of pontocerebellar hypoplasia (PCH), spinal muscular atrophy (SMA), and central nervous system demyelination. Here, we report on four unrelated affected individuals with recessive variants in EXOSC9 and the effect of the variants on the function of the RNA exosome in vitro in affected individuals' fibroblasts and skeletal muscle and in vivo in zebrafish...
May 3, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29726599/the-roles-of-extracellular-vesicle-micrornas-in-the-central-nervous-system
#10
REVIEW
Stephanie N Blandford, Dylan A Galloway, Craig S Moore
MicroRNAs (miRNAs) are small, highly conserved non-coding RNA molecules that post-transcriptionally regulate protein expression and most biological processes. Mature miRNAs are recruited to the RNA-induced silencing complex (RISC) and target mRNAs via complementary base-pairing, thus resulting in translational inhibition and/or transcript degradation. Here, we present evidence implicating miRNAs within extracellular vesicles (EVs), including microvesicles and exosomes, as mediators of central nervous system (CNS) development, homeostasis, and injury...
May 4, 2018: Glia
https://www.readbyqxmd.com/read/29721020/detection-of-hiv-1-and-human-proteins-in-urinary-extracellular-vesicles-from-hiv-patients
#11
Samuel I Anyanwu, Akins Doherty, Michael D Powell, Chamberlain Obialo, Ming B Huang, Alexander Quarshie, Claudette Mitchell, Khalid Bashir, Gale W Newman
Background: Extracellular vesicles (EVs) are membrane bound, secreted by cells, and detected in bodily fluids, including urine, and contain proteins, RNA, and DNA. Our goal was to identify HIV and human proteins (HPs) in urinary EVs from HIV+ patients and compare them to HIV- samples. Methods: Urine samples were collected from HIV+ ( n = 35) and HIV- ( n = 12) individuals. EVs were isolated by ultrafiltration and characterized using transmission electron microscopy, tandem mass spectrometry (LC/MS/MS), and nanoparticle tracking analysis (NTA)...
2018: Advances in Virology
https://www.readbyqxmd.com/read/29718972/structure-of-frequency-interacting-rna-helicase-from-neurospora-crassa-reveals-high-flexibility-in-a-domain-critical-for-circadian-rhythm-and-rna-surveillance
#12
Yalemi Morales, Keith J Olsen, Jacqueline M Bulcher, Sean J Johnson
The FRH (frequency-interacting RNA helicase) protein is the Neurospora crassa homolog of yeast Mtr4, an essential RNA helicase that plays a central role in RNA metabolism as an activator of the nuclear RNA exosome. FRH is also a required component of the circadian clock, mediating protein interactions that result in the rhythmic repression of gene expression. Here we show that FRH unwinds RNA substrates in vitro with a kinetic profile similar to Mtr4, indicating that while FRH has acquired additional functionality, its core helicase function remains intact...
2018: PloS One
https://www.readbyqxmd.com/read/29709702/tumor-released-exosomal-circular-rna-pde8a-promotes-invasive-growth-via-the-mir-338-macc1-met-pathway-in-pancreatic-cancer
#13
Zhonghu Li, Wu Yanfang, Jie Li, Peng Jiang, Tao Peng, Kai Chen, Xin Zhao, Yujun Zhang, Ping Zhen, Jin Zhu, Xiaowu Li
Circular RNA (circ-RNA) and exosomes have recently been shown to play important roles in different tumors. However, the functions and regulatory mechanisms of exosomal circ-RNA in pancreatic ductal adenocarcinoma (PDAC) tumor progression remain unclear. Here, we identified a circular RNA (circ-PDE8A) from liver-metastatic PDAC cells by microarray analysis, detected its expression levels in clinical tissues and found that high circ-PDE8A expression was correlated with lymphatic invasion, TNM stage and a poor survival rate of PDAC patients...
April 27, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29702004/human-trna-derived-small-rnas-modulate-host-oral-microbial-interactions
#14
X He, F Li, B Bor, K Koyano, L Cen, X Xiao, W Shi, D T W Wong
Coevolution of the human host and its associated microbiota has led to sophisticated interactions to maintain a delicate homeostasis. Emerging evidence suggests that in addition to small molecules, peptides, and proteins, small regulatory noncoding RNAs (sRNAs) might play an important role in cross-domain interactions. In this study, we revealed the presence of diverse host transfer RNA-derived small RNAs (tsRNAs) among human salivary sRNAs. We selected 2 tsRNAs (tsRNA-000794 and tsRNA-020498) for further study based on their high sequence similarity to specific tRNAs from a group of Gram-negative oral bacteria, including Fusobacterium nucleatum, a key oral commensal and opportunistic pathogen...
April 1, 2018: Journal of Dental Research
https://www.readbyqxmd.com/read/29696078/newt-cells-secrete-extracellular-vesicles-with-therapeutic-bioactivity-in-mammalian-cardiomyocytes
#15
Ryan C Middleton, Russell G Rogers, Geoffrey De Couto, Eleni Tseliou, Kristin Luther, Ronald Holewinski, Daniel Soetkamp, Jennifer E Van Eyk, Travis J Antes, Eduardo Marbán
Newts can regenerate amputated limbs and cardiac tissue, unlike mammals which lack broad regenerative capacity. Several signaling pathways involved in cell proliferation, differentiation and survival during newt tissue regeneration have been elucidated, however the factors that coordinate signaling between cells, as well as the conservation of these factors in other animals, are not well defined. Here we report that media conditioned by newt limb explant cells (A1 cells) protect mammalian cardiomyocytes from oxidative stress-induced apoptosis...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29689228/exosomes-and-ectosomes-in-intercellular-communication
#16
REVIEW
Jacopo Meldolesi
Exosomes and ectosomes, two distinct types of extracellular vesicles generated by all types of cell, play key roles in intercellular communication. The formation of these vesicles depends on local microdomains assembled in endocytic membranes for exosomes and in the plasma membrane for ectosomes. These microdomains govern the accumulation of proteins and various types of RNA associated with their cytosolic surface, followed by membrane budding inward for exosome precursors and outward for ectosomes. A fraction of endocytic cisternae filled with vesicles - multivesicular bodies - are later destined to undergo regulated exocytosis, leading to the extracellular release of exosomes...
April 23, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29689087/identification-of-rna-binding-proteins-in-exosomes-capable-of-interacting-with-different-types-of-rna-rbp-facilitated-transport-of-rnas-into-exosomes
#17
Luisa Statello, Marco Maugeri, Elena Garre, Muhammad Nawaz, Jessica Wahlgren, Alexandros Papadimitriou, Christina Lundqvist, Lennart Lindfors, Anna Collén, Per Sunnerhagen, Marco Ragusa, Michele Purrello, Cinzia Di Pietro, Natalie Tigue, Hadi Valadi
The RNA that is packaged into exosomes is termed as exosomal-shuttle RNA (esRNA); however, the players, which take this subset of RNA (esRNA) into exosomes, remain largely unknown. We hypothesized that RNA binding proteins (RBPs) could serve as key players in this mechanism, by making complexes with RNAs and transporting them into exosomes during the biosynthesis of exosomes. Here, we demonstrate the presence of 30 RBPs in exosomes that were shown to form RNA-RBP complexes with both cellular RNA and exosomal-RNA species...
2018: PloS One
https://www.readbyqxmd.com/read/29685921/role-of-exosomes-as-a-proinflammatory-mediator-in-the-development-of-ebv-associated-lymphoma
#18
Hiroshi Higuchi, Natsuko Yamakawa, Ken-Ichi Imadome, Takashi Yahata, Ryutaro Kotaki, Jun Ogata, Masatoshi Kakizaki, Koji Fujita, Jun Lu, Kazuaki Yokoyama, Kazuki Okuyama, Ai Sato, Masako Takamatsu, Natsumi Kurosaki, Syakira Mohamad Alba, Azran Azhim, Ryouichi Horie, Toshiki Watanabe, Toshio Kitamura, Kiyoshi Ando, Takao Kashiwagi, Toshimitsu Matsui, Akinao Okamoto, Hiroshi Handa, Masahiko Kuroda, Naoya Nakamura, Ai Kotani
Epstein-Barr virus (EBV) causes various diseases in the elderly including B-cell lymphoma such as Hodgkin's lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). Here, we show that EBV acts in trans on non-infected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between two EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata derived exosomes affected LPD severity possibly through the regulation of macrophage phenotype in vivo...
April 22, 2018: Blood
https://www.readbyqxmd.com/read/29683453/a-blood-based-test-for-the-detection-of-ros1-and-ret-fusion-transcripts-from-circulating-ribonucleic-acid-using-digital-polymerase-chain-reaction
#19
Hestia S Mellert, Kristin E Alexander, Leisa P Jackson, Gary A Pestano
We have developed novel methods for the isolation and characterization of tumor-derived circulating ribonucleic acid (cRNA) for blood-based liquid biopsy. Robust detection of cRNA recovered from blood represents a solution to a critical unmet need in clinical diagnostics. The test begins with the collection of whole blood into blood collection tubes containing preservatives that stabilize cRNA. Cell-free, exosomal, and platelet-associated RNA is isolated from plasma in this test system. The cRNA is reverse transcribed to complementary DNA (cDNA) and amplified using digital polymerase chain reaction (dPCR)...
April 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29679565/activation-of-tlr3-and-its-adaptor-ticam-1-increases-mir-21-levels-in-extracellular-vesicles-released-from-human-cells
#20
Yoshimi Fukushima, Masaaki Okamoto, Kana Ishikawa, Takahisa Kouwaki, Hirotake Tsukamoto, Hiroyuki Oshiumi
Pattern-recognition receptors (PRRs) recognizes viral RNAs and trigger the innate immune responses. Toll-like receptor 3 (TLR3), a PRR, recognizes viral double-stranded RNA (dsRNA) in endolysosomes, whereas cytoplasmic dsRNA is sensed by another PRR, MDA5. TLR3 and MDA5 utilize TICAM-1 and MAVS, respectively, to trigger the signal for inducing innate immune responses. Extracellular vesicles (EVs) include the exosomes and microvesicles; an accumulating body of evidence has shown that EVs delivers functional RNA, such as microRNAs (miRNAs), to other cells and thus mediate intercellular communications...
April 18, 2018: Biochemical and Biophysical Research Communications
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