The Intestinal Microbiota Interferes with the microRNA Response upon Oral Listeria Infection

ABSTRACT The intestinal tract is the largest reservoir of microbes in the human body. The intestinal microbiota is thought to be able to modulate alterations of the gut induced by enteropathogens, thereby maintaining homeostasis. Listeria monocytogenes is the agent of listeriosis, an infection transmitted to humans upon ingestion of contaminated food. Crossing of the intestinal barrier is a critical step of the infection before dissemination into deeper organs. Here, we investigated the role of the intestinal microbiota in the regulation of host protein-coding genes and microRNA (miRNA or miR) expression during Listeria infection. We first established the intestinal miRNA signatures corresponding to the 10 most highly expressed miRNAs in the murine ileum of conventional and germfree mice, noninfected and infected with Listeria. Next, we identified 6 miRNAs whose expression decreased upon Listeria infection in conventional mice. Strikingly, five of these miRNA expression variations (in miR-143, miR-148a, miR-200b, miR-200c, and miR-378) were dependent on the presence of the microbiota. In addition, as is already known, protein-coding genes were highly affected by infection in both conventional and germfree mice. By crossing bioinformatically the predicted targets of the miRNAs to our whole-genome transcriptomic data, we revealed an miRNA-mRNA network that suggested miRNA-mediated global regulation during intestinal infection. Other recent studies have revealed an miRNA response to either bacterial pathogens or commensal bacteria. In contrast, our work provides an unprecedented insight into the impact of the intestinal microbiota on host transcriptional reprogramming during infection by a human pathogen. IMPORTANCE While the crucial role of miRNAs in regulating the host response to bacterial infection is increasingly recognized, the involvement of the intestinal microbiota in the regulation of miRNA expression has not been explored in detail. Here, we investigated the impact of the intestinal microbiota on the regulation of protein-coding genes and miRNA expression in a host infected by L. monocytogenes, a food-borne pathogen. We show that the microbiota interferes with the microRNA response upon oral Listeria infection and identify several protein-coding target genes whose expression correlates inversely with that of the miRNA. Further investigations of the regulatory networks involving miR-143, miR-148a, miR-200b, miR-200c, and miR-378 will provide new insights into the impact of the intestinal microbiota on the host upon bacterial infection.

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Genome Wide Location Analysis Reveals Deregulated MicroRNA Genes In MLL Rearragned Leukemic Genome

Blood ◽

10.1182/blood.v116.21.2507.2507 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2507-2507

Author(s):

Shuangli Mi ◽

Fuhong He ◽

Jun Wu ◽

Jing Zhou ◽

George Wu ◽

...

Keyword(s):

Fusion Protein ◽

Mirna Expression ◽

Expression Profiling ◽

Fusion Proteins ◽

Target Genes ◽

Wild Type ◽

Protein Coding ◽

Protein Coding Genes ◽

Mrna Gene

Abstract Abstract 2507 The MLL (mixed-lineage leukemia) gene encodes a histone methyltransferase that is critical in maintaining gene expression during hematopoiesis. Chromosomal translocations disrupting MLL often leads to the creation of MLL fusion genes that act as potent drivers of acute leukemia. MLL fusion proteins are oncogenic transcription factors that activate the expression of downstream target genes. Expression profiling on patient primary samples and established mouse models has revealed hundreds of protein coding genes which are either up-regulated or down-regulated in MLL associated leukemias. Persistent coexpression of two of those genes, HoxA9 and Meis1, is essential for the initiation and maintenance of MLL leukemia. Our studies have also shown strong association of a microRNA (miRNA) expression signature with MLL- rearranged leukemia, and the expression of several miRNAs were under the control of MLL wild type and fusion proteins. Although profiling of miRNA expression has been reported, the mechanisms underlying deregulated miRNA expression in MLL associated leukemia are poorly understood. Given the role of miRNA as a global suppressor of mRNA gene expression, we hypothesized that the expression of miRNAs could be directly activated by MLL fusion and/or wild type proteins upon MLL gene rearrangement and subsequently down-regulate pertinent target mRNAs to contribute to leukemogenesis. To test our hypothesis in a systematic way, we examined an inducible MLL-ENL-ER transformed mouse cell line, which grow as myeloblastic cells in the presence of MLL-ENL, and differentiate into neutrophils upon inactivation of the fusion protein. Using chromatin immunoprecipitation assay followed by next generation sequencing (ChIP-Seq), we determined whole genome MLL binding pattern in this cellular model. Upon activation of MLL-ENL, 24 miRNAs showed a significant increase in the level of MLL binding (FDR<0.25), suggesting that those genes are directly bound by the MLL-ENL fusion protein. To explore the impact of MLL fusion protein on miRNA and mRNA gene regulation, we performed whole genome expression analysis using Affymetrix mouse microarray in the presence or absence of MLL-ENL. Upon induction of MLL-ENL, the expression levels of 38 miRNAs (out of 609 tiled on the array) were increased, and 57 of 7858 expressed protein-coding genes were down-regulated. An integrative analysis of MLL binding and mRNA/miRNA expression profiling data showed that transcription of three miRNAs were activated upon binding of MLL-ENL, and ten protein coding genes are potential targets of these miRNAs. We are currently exploring the role of these three miRNAs and their respective mRNA target genes in leukemogenesis using in vitro and in vivo models. Taken together, our data suggest that MLL fusion protein may play an important role in leukemogenesis by promoting miRNA transcription, which subsequently inhibit the expression of critical mRNA target genes. Our study provides a basis to further explore the regulatory network involving MLL fusion protein and its key miRNA target genes in the leukemic genome. Disclosures: No relevant conflicts of interest to declare.

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RNA sequencing analysis of altered expression of long noncoding RNAs associated with Schistosoma japonicum infection in the murine liver and spleen

Parasites & Vectors ◽

10.1186/s13071-020-04457-9 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Tianqi Xia ◽

Bikash Ranjan Giri ◽

Jingyi Liu ◽

Pengfei Du ◽

Xue Li ◽

...

Keyword(s):

Rna Sequencing ◽

Schistosoma Japonicum ◽

Target Genes ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Differentially Expressed ◽

Protein Coding ◽

Altered Expression ◽

Protein Coding Genes

Abstract Background Schistosomiasis is a chronic, debilitating infectious disease caused by members of the genus Schistosoma. Previous findings have suggested a relationship between infection with Schistosoma spp. and alterations in the liver and spleen of infected animals. Recent reports have shown the regulatory role of noncoding RNAs, such as long noncoding RNAs (lncRNAs), in different biological processes. However, little is known about the role of lncRNAs in the mouse liver and spleen during Schistosoma japonicum infection. Methods In this study, we identified and investigated lncRNAs using standard RNA sequencing (RNA-Seq). The biological functions of the altered expression of lncRNAs and their target genes were predicted using bioinformatics. Ten dysregulated lncRNAs were selected randomly and validated in reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) experiments. Results Our study identified 29,845 and 33,788 lncRNAs from the liver and spleen, respectively, of which 212 were novel lncRNAs. We observed that 759 and 789 of the lncRNAs were differentially expressed in the respective organs. The RT-qPCR results correlated well with the sequencing data. In the liver, 657 differentially expressed lncRNAs were predicted to target 2548 protein-coding genes, whereas in the spleen 660 differentially expressed lncRNAs were predicted to target 2673 protein-coding genes. Moreover, functional annotation showed that the target genes of the differentially expressed lncRNAs were associated with cellular processes, metabolic processes, and binding, and were significantly enriched in metabolic pathways, the cell cycle, ubiquitin-mediated proteolysis, and pathways in cancer. Conclusions Our study showed that numerous lncRNAs were differentially expressed in S. japonicum-infected liver and spleen compared to control liver and spleen; this suggested that lncRNAs may be involved in pathogenesis in the liver and spleen during S. japonicum infection.

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Contribution of Retrotransposition to Developmental Disorders

10.1101/471375 ◽

2018 ◽

Cited By ~ 2

Author(s):

Eugene J. Gardner ◽

Elena Prigmore ◽

Giuseppe Gallone ◽

Petr Danecek ◽

Kaitlin E. Samocha ◽

...

Keyword(s):

Developmental Disorders ◽

De Novo ◽

Purifying Selection ◽

Mobile Genetic Elements ◽

Protein Coding ◽

Protein Coding Genes ◽

Genome Wide ◽

The Impact ◽

Transcribed Sequences

AbstractMobile genetic Elements (MEs) are segments of DNA which, through an RNA intermediate, can generate new copies of themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. As such, we have identified RT-derived events in 9,738 exome sequenced trios with DD-affected probands as part of the Deciphering Developmental Disorders (DDD) study. We have ascertained 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04% of probands), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we have estimated genome-wide germline ME mutagenesis and constraint and demonstrated that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.

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Ovule siRNAs methylate and silence protein-coding genes in trans

10.1101/2021.06.10.447945 ◽

2021 ◽

Author(s):

Diane Burgess ◽

Hiu Tung Chow ◽

Jeffrey W Grover ◽

Michael Freeling ◽

Rebecca A Mosher

Keyword(s):

Dna Methylation ◽

Target Genes ◽

Consensus Sequence ◽

Transcriptional Silencing ◽

Protein Coding ◽

Protein Coding Genes ◽

Developing Seed ◽

In Trans ◽

Direct Targeting

24-nt small interfering siRNAs maintain asymmetric DNA methylation at thousands of euchromatic transposable elements in plant genomes in a process call RNA-directed DNA Methylation (RdDM). Although this methylation occasionally causes transcriptional silencing of nearby protein-coding genes, direct targeting of methylation at coding sequences is rare. RdDM is dispensable for growth and development in Arabidopsis, but is required for reproduction in other plant species, such as Brassica rapa. 24-nt siRNAs are particularly abundant in reproductive tissue, due largely to overwhelming expression from a small number of loci in the ovule and developing seed coat, termed siren loci. Here we show that siRNAs are often produced from gene fragments embedded in siren loci, and that these siRNAs can trigger methylation in trans at related protein-coding genes. This trans-methylation is associated with transcriptional silencing of target genes and may be responsible for seed abortion in RdDM mutants. Furthermore, we demonstrate that a consensus sequence in at least two families of DNA transposons is associated with abundant siren expression, most likely through recruitment of the CLSY3 putative chromatin remodeller. This research describes a new mechanism whereby RdDM influences gene expression and sheds light on the role of RdDM during plant reproduction.

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Antisense Transcription Is Pervasive but Rarely Conserved in Enteric Bacteria

mBio ◽

10.1128/mbio.00156-12 ◽

2012 ◽

Vol 3 (4) ◽

Cited By ~ 91

Author(s):

Rahul Raghavan ◽

Daniel B. Sloan ◽

Howard Ochman

Keyword(s):

Noncoding Rnas ◽

Enteric Bacteria ◽

Antisense Transcription ◽

Antisense Transcripts ◽

Protein Coding ◽

Content Type ◽

Protein Coding Genes ◽

Genome Wide ◽

Serovar Typhimurium

ABSTRACT Noncoding RNAs, including antisense RNAs (asRNAs) that originate from the complementary strand of protein-coding genes, are involved in the regulation of gene expression in all domains of life. Recent application of deep-sequencing technologies has revealed that the transcription of asRNAs occurs genome-wide in bacteria. Although the role of the vast majority of asRNAs remains unknown, it is often assumed that their presence implies important regulatory functions, similar to those of other noncoding RNAs. Alternatively, many antisense transcripts may be produced by chance transcription events from promoter-like sequences that result from the degenerate nature of bacterial transcription factor binding sites. To investigate the biological relevance of antisense transcripts, we compared genome-wide patterns of asRNA expression in closely related enteric bacteria, Escherichia coli and Salmonella enterica serovar Typhimurium, by performing strand-specific transcriptome sequencing. Although antisense transcripts are abundant in both species, less than 3% of asRNAs are expressed at high levels in both species, and only about 14% appear to be conserved among species. And unlike the promoters of protein-coding genes, asRNA promoters show no evidence of sequence conservation between, or even within, species. Our findings suggest that many or even most bacterial asRNAs are nonadaptive by-products of the cell’s transcription machinery. IMPORTANCE Application of high-throughput methods has revealed the expression throughout bacterial genomes of transcripts encoded on the strand complementary to protein-coding genes. Because transcription is costly, it is usually assumed that these transcripts, termed antisense RNAs (asRNAs), serve some function; however, the role of most asRNAs is unclear, raising questions about their relevance in cellular processes. Because natural selection conserves functional elements, comparisons between related species provide a method for assessing functionality genome-wide. Applying such an approach, we assayed all transcripts in two closely related bacteria, Escherichia coli and Salmonella enterica serovar Typhimurium, and demonstrate that, although the levels of genome-wide antisense transcription are similarly high in both bacteria, only a small fraction of asRNAs are shared across species. Moreover, the promoters associated with asRNAs show no evidence of sequence conservation between, or even within, species. These findings indicate that despite the genome-wide transcription of asRNAs, many of these transcripts are likely nonfunctional.

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Complete Genome Sequence of Cupriavidus necator H16 (DSM 428)

Microbiology Resource Announcements ◽

10.1128/mra.00814-19 ◽

2019 ◽

Vol 8 (37) ◽

Cited By ~ 2

Author(s):

Gareth T. Little ◽

Muhammad Ehsaan ◽

Christian Arenas-López ◽

Kamran Jawed ◽

Klaus Winzer ◽

...

Keyword(s):

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Cupriavidus Necator ◽

Rrna Genes ◽

Trna Genes ◽

Protein Coding ◽

Content Type ◽

Protein Coding Genes ◽

Cupriavidus Necator H16

The hydrogen-utilizing strain Cupriavidus necator H16 (DSM 428) was sequenced using a combination of PacBio and Illumina sequencing. Annotation of this strain reveals 6,543 protein-coding genes, 263 pseudogenes, 64 tRNA genes, and 15 rRNA genes.

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Social capital and national innovation system: a cross-country analysis

Cross Cultural Management An International Journal ◽

10.1108/ccm-10-2013-0154 ◽

2014 ◽

Vol 21 (4) ◽

pp. 453-475 ◽

Cited By ~ 9

Author(s):

Sepehr Ghazinoory ◽

Ali Bitaab ◽

Ardeshir Lohrasbi

Keyword(s):

Social Capital ◽

National Level ◽

Innovation System ◽

Negative Effects ◽

Content Type ◽

Research Findings ◽

Different Dimensions ◽

The Impact ◽

Positive Effect

Purpose – In the last two decades, researchers have paid much attention to the role of cultural values on economic and social development. In particular, the crucial role of different aspects of culture on the development of innovation has been stressed in the literature. Consequently, it is vital to understand how social capital, as a core cultural value, affects the innovation process and the innovative performance at the national level. However, to date, the impact of different dimensions of social capital and innovation has not been properly portrayed or explained. Thus, the purpose of this paper is to investigate the influence of four different dimensions of social capital (institutional and interpersonal, associational life and norms) on two of the main functions of national innovation system (NIS) (entrepreneurship and knowledge creation) based on over 50,000 observations in 34 countries. Design/methodology/approach – In this regard, national-level data from the World Values Survey database was employed to quantify social capital. Entrepreneurship is, in turn, assumed to consist of three sub-indexes and 14 indicators based on the Global Entrepreneurship Index. Knowledge creation is also measured through US Patent Office applications. Also, exploratory factor analysis and structural equation modeling approach were used to build the measurement model and investigate the impact that each factor of social capital had on entrepreneurship and knowledge application, respectively. Measurement and structural models were built and their reliability and validity were tested using various fit indices. Research findings suggest the strong positive effect of institutional trust and networking on entrepreneurship. Also, interpersonal trust and networks were shown to have high influence on knowledge development at the national level. Norms appear to have naïve to medium negative effects on both functions. Findings – Research findings suggest the strong positive effect of institutional trust and networking on entrepreneurship. Also, interpersonal trust and networks were shown to have high influence on knowledge development at the national level. Norms appear to have naïve to medium negative effects on both functions. Originality/value – However, to date, the impact of different dimensions of social capital and innovation has not been properly portrayed or explained.

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Market orientation, innovation commercialization capability and firm performance relationships: the moderating role of supply chain influence

Journal of Business and Industrial Marketing ◽

10.1108/jbim-10-2016-0238 ◽

2017 ◽

Vol 32 (7) ◽

pp. 913-924 ◽

Cited By ~ 12

Author(s):

Jeen-Su Lim ◽

William K. Darley ◽

David Marion

Keyword(s):

Supply Chain ◽

Firm Performance ◽

Market Orientation ◽

Innovation Management ◽

Strategy Formulation ◽

Content Type ◽

Positive Effects ◽

The Impact ◽

Moderating Role

Purpose The study aims to explore supply chain influence (SCI) on the linkages among market orientation, innovation capabilities and firm performance (FP), using the resource-based view as a theoretical backdrop. Design Survey data from 182 top managers who are involved in strategy formulation and innovative direction of their companies was collected and analyzed using moderated multiple regression analysis. Findings Results revealed a moderating role of the SCI in that the proactive market orientation (PMO) and FP relationship is stronger when SCI is high, and innovation commercialization capability (ICC) and FP relationship is stronger when SCI is low. Practical implications Firms pursuing high PMO strategy must collaborate with supply chain function to achieve the full effect of PMO. Additionally, as supply chain is critical to meeting customers’ needs, these firms should allow supply chain to exert greater influence to enjoy the positive effects of PMO in addition to ensuring full integration into marketing strategy implementation. Also, firms with high ICC need to limit SCI to maximize the benefit of ICC on FP, just as innovation management needs to be cognizant of other functional areas. Originality/value The study investigates the potential moderating role of SCI on the relationships among market orientation, ICC and FP. The study fills a gap in the understanding of the nature and role of supply chain in the marketing–supply chain interaction, and the impact on FP.

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Handling negative publicity

Journal of Communication Management ◽

10.1108/jcom-11-2016-0091 ◽

2017 ◽

Vol 21 (3) ◽

pp. 267-286 ◽

Cited By ~ 7

Author(s):

Angie Chung ◽

Hua Jiang

Keyword(s):

Network Theory ◽

Design Methodology ◽

Content Type ◽

Csr Communication ◽

Subject Design ◽

Negative Publicity ◽

Associative Network Theory ◽

Corporate Social ◽

The Impact

Purpose Based on the framing theory and the associative network theory, the purpose of this paper is to develop and test a model that examines the impact of employing corporate social responsibility (CSR) communication in apology statements after negative publicity. Specifically, this study examines the role of CSR fit and CSR history in reducing anger and negative word-of-mouth (NWOM). This study also examines whether perceived CSR motivation and skepticism toward the apology statement mediate the effect of CSR fit and CSR history on anger and NWOM. Design/methodology/approach This study was a 2×2 between-subject design manipulating CSR fit (high or low) and CSR history (long or short). Findings The findings of this study suggest that strategically employing CSR communication in an apology statement after negative publicity may reduce negative consumer reactions. Originality/value The effects of CSR history and CSR fit have been studied in different contexts, but the effects of mentioning the two components in terms of apology statements had been understudied. This paper fulfills an identified need to study how employing CSR communication in apology statements after negative publicity can mitigate negative audience reactions.

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Managing multichannel coordination in retail banking: the influence of customer participation

International Journal of Bank Marketing ◽

10.1108/02652320610681756 ◽

2006 ◽

Vol 24 (5) ◽

pp. 327-345 ◽

Cited By ~ 15

Author(s):

Loïc Plé

Keyword(s):

Organizational Design ◽

Retail Banking ◽

Customer Participation ◽

Content Type ◽

Quantitative Studies ◽

Retail Banks ◽

The Impact ◽

Depth Interviews

PurposeThe purpose of this research is to explore the combining of marketing and organizational literature. This paper seeks to evaluate the relationships between multichannel coordination and customer participation, as seen through the lens of potential customer opportunism. It aims at showing the impact of this opportunism on the organizational design of multiple channels structures.Design/methodology/approachThe research reports on an exploratory case study in a French retail bank. A total of 25 in‐depth interviews were conducted, and the use of other sources enabled data triangulation.FindingsThe results show first that an increase in the number of distribution channels is liable to favor customer opportunistic behavior. To counter this, the bank mainly relies on impersonal coordination modes. An emerging result highlights the role of the customer as a “perceptual filter” between the different channels of employees.Research limitations/implicationsCustomer opportunism is studied via channels employees perceptions. An investigation using a customer survey may help to better understand this construct, e.g. to identify its antecedents, and to measure it precisely. Moreover, further qualitative and/or quantitative studies with larger sample sizes are needed to try and generalize these results.Practical implicationsIt is recommended not to forget that customers can facilitate or hinder multichannel coordination. Retail banks have the power to use them conveniently, provided that they are fully conscious of the scope of the “partial employee” role played by the customer.Originality/valueThis paper broadens understanding of how multichannel distribution structures are coordinated, and in a way belies traditional organizational design literature. The emerging result gives birth to the concept of “reversed interactive marketing”, which has interesting theoretical and practical repercussions.

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