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exosome and RNA sequence

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https://www.readbyqxmd.com/read/27917920/transcriptome-and-long-noncoding-rna-sequencing-of-three-extracellular-vesicle-subtypes-released-from-the-human-colon-cancer-lim1863-cell-line
#1
Maoshan Chen, Rong Xu, Hong Ji, David W Greening, Alin Rai, Keiichi Izumikawa, Hideaki Ishikawa, Nobuhiro Takahashi, Richard J Simpson
Previously we reported that LIM1863 colorectal cancer (CRC) cells secrete three distinct extracellular vesicle subtypes - two subpopulations of exosomes (apical EpCAM-Exos and basolateral A33-Exos) and shed microvesicles (sMVs) - with distinct protein and miRNA signatures. Here, we extend our omics approach to understand the fundamental role of LIM1863-derived EVs by performing a comprehensive analysis of their mRNAs and long non-coding RNAs (lncRNAs) using RNA-Seq. We show that 2,389 mRNAs, 317 pseudogene transcripts, 1,028 lncRNAs and 206 short non-coding RNAs selectively distributed to (i...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27872161/identification-of-urinary-exosomal-non-coding-rnas-as-novel-biomarkers-in-chronic-kidney-disease
#2
Rimpi Khurana, Glory Ranches, Simon Schafferer, Melanie Lukasser, Michael Rudnicki, Gert Mayer, Alexander Hüttenhofer
In chronic kidney disease (CKD), the decline in glomerular filtration rate is associated with increased morbidity and mortality and thus poses a major challenge for healthcare systems. While the contribution of tissue-derived miRNAs and mRNAs to CKD progression has extensively been studied, little is known about the role of urinary exosomes and their association with CKD. Exosomes are small, membrane-derived endocytic vesicles that contribute to cell-to-cell communication and are present in various body fluids, such as blood or urine...
November 21, 2016: RNA
https://www.readbyqxmd.com/read/27858503/high-throughput-sequencing-of-two-populations-of-extracellular-vesicles-provides-an-mrna-signature-that-can-be-detected-in-the-circulation-of-breast-cancer-patients
#3
Andrew Conley, Valentina R Minciacchi, Dhong Hyun Lee, Beatrice S Knudsen, Beth Y Karlan, Luigi Citrigno, Giuseppe Viglietto, Muneesh Tewari, Michael R Freeman, Francesca Demichelis, Dolores Di Vizio
Extracellular vesicles (EVs) contain a wide range of RNA types with a reported prevalence of non-coding RNA. To date a comprehensive characterization of the protein coding transcripts in EVs is still lacking. We performed RNA-Sequencing (RNA-Seq) of two EV populations and identified a small fraction of transcripts that were expressed at significantly different levels in large oncosomes and exosomes, suggesting they may mediate specialized functions. However, these two EV populations exhibited a common mRNA signature that, in comparison to their donor cells, was significantly enriched in mRNAs encoding E2F transcriptional targets and histone proteins...
November 18, 2016: RNA Biology
https://www.readbyqxmd.com/read/27799337/small-rna-sequencing-in-cells-and-exosomes-identifies-eqtls-and-14q32-as-a-region-of-active-export
#4
Emily K Tsang, Nathan S Abell, Xin Li, Vanessa Anaya, Konrad J Karczewski, David A Knowles, Raymond G Sierra, Kevin S Smith, Stephen B Montgomery
Exosomes are small extracellular vesicles that carry heterogeneous cargo, including RNA, between cells. Increasing evidence suggests that exosomes are important mediators of intercellular communication and biomarkers of disease. Despite this, the variability of exosomal RNA between individuals has not been well quantified. To assess this variability, we sequenced the small RNA of cells and exosomes from a 17-member family. Across individuals, we show that selective export of miRNAs occurs not only at the level of specific transcripts, but that a cluster of 74 mature miRNAs on chromosome 14q32 is massively exported in exosomes while mostly absent from cells...
October 31, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/27791479/two-distinct-extracellular-rna-signatures-released-by-a-single-cell-type-identified-by-microarray-and-next-generation-sequencing
#5
Cecilia Lässer, Ganesh Vilas Shelke, Ashish Yeri, Dae-Kyum Kim, Rossella Crescitelli, Stefania Raimondo, Margareta Sjöstrand, Yong Song Gho, Kendall Van Keuren Jensen, Jan Lötvall
Cells secrete extracellular RNA (exRNA) to their surrounding environment and exRNA has been found in many body fluids such as blood, breast milk and cerebrospinal fluid. However, there are conflicting results regarding the nature of exRNA. Here, we have separated two distinct exRNA profiles released by mast cells, here termed high-density (HD) and low-density (LD) exRNA. The exRNA in both fractions was characterized by microarray and next-generation sequencing. Both exRNA fractions contained mRNA and miRNA, and the mRNAs in the LD exRNA correlated closely with the cellular mRNA, whereas the HD mRNA did not...
October 28, 2016: RNA Biology
https://www.readbyqxmd.com/read/27788488/serum-exosomal-mir-4772-3p-is-a-predictor-of-tumor-recurrence-in-stage-ii-and-iii-colon-cancer
#6
Chang Liu, Cathy Eng, Jianjun Shen, Yue Lu, Takata Yoko, Amir Mehdizadeh, George J Chang, Miguel A Rodriguez-Bigas, Yanan Li, Ping Chang, Yixiang Mao, Manal M Hassan, Fangyu Wang, Donghui Li
PURPOSE: The study was aimed to evaluate the prognostic or predictive value of serum exosomal microRNAs (miRNAs) for tumor recurrence and response to adjuvant therapy in stage II and stage III colon cancer. RESULTS: 145 differentially expressed mature miRNAs were identified (P<0.05) and 10 top hits were carried forward in validation test. MiR-4772-3p was significantly under-expressed in 27 patients with recurrence compared to in 57 patients without recurrence (P=0...
October 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27780738/next-generation-sequencing-based-small-rna-profiling-of-cerebrospinal-fluid-exosomes
#7
Yohsuke Yagi, Takuya Ohkubo, Hideya Kawaji, Akira Machida, Haruka Miyata, Saori Goda, Sugata Roy, Yoshihide Hayashizaki, Harukazu Suzuki, Takanori Yokota
MicroRNAs (miRNAs), particularly those found in human body fluids, have been suggested as potential biomarkers. Among various body fluids, the cerebrospinal fluid (CSF) shows promise as a profiling target for diagnosis and monitoring of neurological diseases. However, relevant genome-scale studies are limited and no studies have profiled exosomal miRNAs in CSF. Therefore, we conducted a next-generation sequencing-based genome-wide survey of small RNAs in the exosomal and non-exosomal (supernatant) fractions of healthy human CSF as well as serum in each donor...
October 22, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27760749/circulating-mirnas-as-potential-alternative-cell-signaling-associated-with-maternal-recognition-of-pregnancy-in-the-mare
#8
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
https://www.readbyqxmd.com/read/27758893/genome-wide-mapping-of-uncapped-and-cleaved-transcripts-reveals-a-role-for-the-nuclear-mrna-cap-binding-complex-in-cotranslational-rna-decay-in-arabidopsis
#9
Xiang Yu, Matthew R Willmann, Stephen J Anderson, Brian D Gregory
RNA turnover is necessary for controlling proper mRNA levels posttranscriptionally. 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 multisubunit exosome complex. Here, we use genome-wide mapping of uncapped and cleaved transcripts to reveal the global landscape of cotranslational mRNA decay in the Arabidopsis thaliana transcriptome. We found that this process leaves a clear three nucleotide periodicity in open reading frames...
October 2016: Plant Cell
https://www.readbyqxmd.com/read/27732855/the-rna-binding-protein-syncrip-is-a-component-of-the-hepatocyte-exosomal-machinery-controlling-microrna-sorting
#10
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
https://www.readbyqxmd.com/read/27711183/xrn1-is-a-species-specific-virus-restriction-factor-in-yeasts
#11
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
https://www.readbyqxmd.com/read/27608715/plasma-exosome-micrornas-are-indicative-of-breast-cancer
#12
Bethany N Hannafon, Yvonne D Trigoso, Cameron L Calloway, Y Daniel Zhao, David H Lum, Alana L Welm, Zhizhuang J Zhao, Kenneth E Blick, William C Dooley, W Q Ding
BACKGROUND: microRNAs are promising candidate breast cancer biomarkers due to their cancer-specific expression profiles. However, efforts to develop circulating breast cancer biomarkers are challenged by the heterogeneity of microRNAs in the blood. To overcome this challenge, we aimed to develop a molecular profile of microRNAs specifically secreted from breast cancer cells. Our first step towards this direction relates to capturing and analyzing the contents of exosomes, which are small secretory vesicles that selectively encapsulate microRNAs indicative of their cell of origin...
2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27601730/aml-suppresses-hematopoiesis-by-releasing-exosomes-that-contain-micrornas-targeting-c-myb
#13
Noah I Hornick, Ben Doron, Sherif Abdelhamed, Jianya Huan, Christina A Harrington, Rongkun Shen, Xiaolu A Cambronne, Santhosh Chakkaramakkil Verghese, Peter Kurre
Exosomes are paracrine regulators of the tumor microenvironment and contain complex cargo. We previously reported that exosomes released from acute myeloid leukemia (AML) cells can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors. We found that the systemic loss of hematopoietic function is also in part a consequence of AML exosome-directed microRNA (miRNA) trafficking to HSPCs. Exosomes isolated from cultured AML or the plasma from mice bearing AML xenografts exhibited enrichment of miR-150 and miR-155...
September 6, 2016: Science Signaling
https://www.readbyqxmd.com/read/27582331/next-generation-sequencing-of-protein-coding-and-long-non-protein-coding-rnas-in-two-types-of-exosomes-derived-from-human-whole-saliva
#14
Yuko Ogawa, Masafumi Tsujimoto, Ryohei Yanoshita
Exosomes are small extracellular vesicles containing microRNAs and mRNAs that are produced by various types of cells. We previously used ultrafiltration and size-exclusion chromatography to isolate two types of human salivary exosomes (exosomes I, II) that are different in size and proteomes. We showed that salivary exosomes contain large repertoires of small RNAs. However, precise information regarding long RNAs in salivary exosomes has not been fully determined. In this study, we investigated the compositions of protein-coding RNAs (pcRNAs) and long non-protein-coding RNAs (lncRNAs) of exosome I, exosome II and whole saliva (WS) by next-generation sequencing technology...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27580880/functional-characterization-of-a-chr13q22-1-pancreatic-cancer-risk-locus-reveals-long-range-interaction-and-allele-specific-effects-on-dis3-expression
#15
Jason W Hoskins, Abdisamad Ibrahim, Mickey A Emmanuel, Sarah M Manmiller, Yinglun Wu, Maura O'Neill, Jinping Jia, Irene Collins, Mingfeng Zhang, Janelle V Thomas, Lauren M Rost, Sudipto Das, Hemang Parikh, Jefferson M Haake, Gail L Matters, Robert C Kurtz, William R Bamlet, Alison Klein, Rachael Stolzenberg-Solomon, Brian M Wolpin, Ronit Yarden, Zhaoming Wang, Jill Smith, Sara H Olson, Thorkell Andresson, Gloria M Petersen, Laufey T Amundadottir
Genome-wide association studies (GWAS) have identified multiple common susceptibility loci for pancreatic cancer. Here we report fine-mapping and functional analysis of one such locus residing in a 610 kb gene desert on chr13q22.1 (marked by rs9543325). The closest candidate genes, KLF5, KLF12, PIBF1, DIS3 and BORA, range in distance from 265-586 kb. Sequencing three sub-regions containing the top ranked SNPs by imputation P-value revealed a 30 bp insertion/deletion (indel) variant that was significantly associated with pancreatic cancer risk (rs386772267, P = 2...
August 30, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27402898/relative-contributions-of-the-structural-and-catalytic-roles-of-rrp6-in-exosomal-degradation-of-individual-mrnas
#16
Kaustav Mukherjee, Justin Gardin, Bruce Futcher, Janet Leatherwood
The RNA exosome is a conserved complex for RNA degradation with two ribonucleolytic subunits, Dis3 and Rrp6. Rrp6 is a 3'-5' exonuclease, but it also has a structural role in helping target RNAs to the Dis3 activity. The relative importance of the exonuclease activity and the targeting activity probably differs between different RNA substrates, but this is poorly understood. To understand the relative contributions of the exonuclease and the targeting activities to the degradation of individual RNA substrates in Schizosaccharomyces pombe, we compared RNA levels in an rrp6 null mutant to those in an rrp6 point mutant specifically defective in exonuclease activity...
September 2016: RNA
https://www.readbyqxmd.com/read/27396686/intracellular-and-extracellular-microrna-an-update-on-localization-and-biological-role
#17
Julia A Makarova, Maxim U Shkurnikov, Daniel Wicklein, Tobias Lange, Timur R Samatov, Andrey A Turchinovich, Alexander G Tonevitsky
MicroRNA (miRNA) is a class of small non-coding RNAs which mediate post-transcriptional gene silencing (PTGS) by sequence-specific inhibition of target mRNAs translation and/or lowering their half-lives in the cytoplasm. Together with their binding partners, Argonaute (AGO) proteins, miRNAs form cores of RNA-induced silencing complexes (RISC). Despite a substantial progress in understanding RISC structure, until recently little was known about its localization in the cell. This review is aimed to provide an overview of the emerging picture of miRNA and RISC localization and function both in the intracellular space and outside of the cell...
June 25, 2016: Progress in Histochemistry and Cytochemistry
https://www.readbyqxmd.com/read/27388239/umbilical-cord-derived-mesenchymal-stem-cell-derived-exosomal-micrornas-suppress-myofibroblast-differentiation-by-inhibiting-the-transforming-growth-factor-%C3%AE-smad2-pathway-during-wound-healing
#18
Shuo Fang, Chen Xu, Yuntong Zhang, Chunyu Xue, Chao Yang, Hongda Bi, Xijing Qian, Minjuan Wu, Kaihong Ji, Yunpeng Zhao, Yue Wang, Houqi Liu, Xin Xing
: : Excessive scar formation caused by myofibroblast aggregations is of great clinical importance during skin wound healing. Studies have shown that mesenchymal stem cells (MSCs) can promote skin regeneration, but whether MSCs contribute to scar formation remains undefined. We found that umbilical cord-derived MSCs (uMSCs) reduced scar formation and myofibroblast accumulation in a skin-defect mouse model. We found that these functions were mainly dependent on uMSC-derived exosomes (uMSC-Exos) and especially exosomal microRNAs...
July 7, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27345150/structure-of-a-cytoplasmic-11-subunit-rna-exosome-complex
#19
Eva Kowalinski, Alexander Kögel, Judith Ebert, Peter Reichelt, Elisabeth Stegmann, Bianca Habermann, Elena Conti
The RNA exosome complex associates with nuclear and cytoplasmic cofactors to mediate the decay, surveillance, or processing of a wide variety of transcripts. In the cytoplasm, the conserved core of the exosome (Exo10) functions together with the conserved Ski complex. The interaction of S. cerevisiae Exo10 and Ski is not direct but requires a bridging cofactor, Ski7. Here, we report the 2.65 Å resolution structure of S. cerevisiae Exo10 bound to the interacting domain of Ski7. Extensive hydrophobic interactions rationalize the high affinity and stability of this complex, pointing to Ski7 as a constitutive component of the cytosolic exosome...
July 7, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27338352/spatial-partitioning-of-mirnas-is-related-to-sequence-similarity-in-overall-transcriptome
#20
William Seffens, Fisseha Abebe, Chad Evans, Xiao-Qian Wang
RNAs have been shown to exhibit differential enrichment between nuclear, cytoplasmic, and exosome fractions. A current fundamental question asks why non-coding RNA partition into different spatial compartments. We report on the analysis of cellular compartment models with miRNA data sources for spatial-mechanistic modeling to address the broad area of multi-scalar cellular communication by miRNAs. We show that spatial partitioning of miRNAs is related to sequence similarity to the overall transcriptome. This has broad implications in biological informatics for gene regulation and provides a deeper understanding of nucleotide sequence structure and RNA language meaning for human pathologies resulting from changes in gene expression...
2016: International Journal of Molecular Sciences
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