Article

The mammalian microRNA response to bacterial infections

Institute for Molecular Infection Biology (IMIB) and Research Centre for Infection Diseases (ZINF), University of Würzburg
RNA biology (Impact Factor: 4.97). 06/2012; 9(6):742-50. DOI: 10.4161/rna.20018
Source: PubMed

ABSTRACT

MicroRNAs are small RNAs that post-transcriptionally regulate eukaryotic gene expression. In addition to their involvement in a wide range of physiological and pathological processes, including viral infections, microRNAs are increasingly implicated in the eukaryotic response to bacterial pathogens. Recent studies have characterized changes in host microRNA expression following infection with exclusively extracellular (Helicobacter pylori) or intracellular (Salmonella enterica) Gram-negative bacteria, as well as in the response to Gram-positive (Listeria monocytogenes) and other pathogens (Mycobacterium and Francisella species). In this review, we discuss the emerging roles of microRNAs in mammalian host signaling and defense against bacterial pathogens.

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    • "MicroRNAs are 19e22 nucleotides complementary region to the target mRNA leading to protein translation silencing. Although early studies were focused on the role of miRNAs during viral and parasitic infections [1] [2], the crucial role of miRNAs in the interplay between host and bacteria has been assessed as well [3]. Not * Corresponding author. "
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    ABSTRACT: MicroRNAs are a class of small non-coding RNAs that have emerged as key regulators of gene expression at the post-transcriptional level by sequence-specific binding to target mRNAs. Some microRNAs block translation, while others promote mRNA degradation, leading to a reduction in protein availability. A single miRNA can potentially regulate the expression of multiple genes and their encoded proteins. Therefore, miRNAs can influence molecular signalling pathways and regulate many biological processes in health and disease. Upon infection, host cells rapidly change their transcriptional programs, including miRNA expression, as a response against the invading microorganism. Not surprisingly, pathogens can also alter the host miRNA profile to their own benefit, which is of major importance to scientists addressing high morbidity and mortality infectious diseases such as tuberculosis. In this review, we present recent findings on the miRNAs regulation of the host response against mycobacterial infections, providing new insights into host-pathogen interactions. Understanding these findings and its implications could reveal new opportunities for designing better diagnostic tools, therapies and more effective vaccines.
    Full-text · Article · Dec 2015
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    • "MiRNAs have also been shown to play crucial roles during infection by diverse pathogens, including viruses, parasites and bacteria (reviewed in [13] [14] [15]). Seminal work on the role of miRNAs in hostpathogen interactions focused on virus infections. "
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    ABSTRACT: MicroRNAs are small non-coding RNAs with a central role in the post-transcriptional control of gene expression, that have been implicated in a wide-range of biological processes. Regulation of miRNA expression is increasingly recognized as a crucial part of the host response to infection by bacterial pathogens, as well as a novel molecular strategy exploited by bacteria to manipulate host cell pathways. Here, we review the current knowledge of bacterial pathogens that modulate host microRNA expression, focusing on mammalian host cells, and the implications of microRNAs (miRNA) regulation on the outcome of infection. The emerging role of commensal bacteria, as part of the gut microbiota, on host miRNA expression in the presence or absence of bacterial pathogens is also discussed.
    Full-text · Article · Aug 2014 · FEBS Letters
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    • "It has recently been reported that miRNAs can sense biotic stresses operating as an integral part of host immune responses to microbial infections, caused by viral, bacterial and Apicomplexan pathogens [22–24]. Interestingly, in A. gambiae the upstream control regions of the major components of miRNA biogenesis, Drosha, Dcr-1 and Ago-1 are enriched in the potential binding sites for NF-kappaB-related transcription factors [10], presumably providing a link between the miRNA pathway and immune responses. "
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    ABSTRACT: Background: microRNAs (miRNAs) are a highly abundant class of small noncoding regulatory RNAs that post-transcriptionally regulate gene expression in multicellular organisms. miRNAs are involved in a wide range of biological and physiological processes, including the regulation of host immune responses to microbial infections. Small-scale studies of miRNA expression in the malaria mosquito Anopheles gambiae have been reported, however no comprehensive analysis of miRNAs has been performed so far. Results: Using small RNA sequencing, we characterized de novo A. gambiae miRNA repertoire expressed in adult sugar- and blood-fed females. We provided transcriptional evidences for 123 miRNAs, including 58 newly identified miRNAs. Out of the newly described miRNAs, 19 miRNAs are homologs to known miRNAs in other insect species and 17 miRNAs share sequence similarity restricted to the seed sequence. The remaining 21 novel miRNAs displayed no obvious sequence homology with known miRNAs. Detailed bioinformatics analysis of the mature miRNAs revealed a sequence variation occurring at their 5'-end and leading to functional seed shifting in more than 5% of miRNAs. We also detected significant sequence heterogeneity at the 3'-ends of the mature miRNAs, mostly due to imprecise processing and post-transcriptional modifications. Comparative analysis of arm-switching events revealed the existence of species-specific production of dominant mature miRNAs induced by blood feeding in mosquitoes. We also identified new conserved and fragmented miRNA clusters and A. gambiae-specific miRNA gene duplication. Using miRNA expression profiling, we identified the differentially expressed miRNAs at an early time point after regular blood feeding and after infection with the rodent malaria parasite Plasmodium berghei. Significant changes were detected in the expression levels of 4 miRNAs in blood-fed mosquitoes, whereas 6 miRNAs were significantly upregulated after P. berghei infection. Conclusions: In the current study, we performed the first systematic analysis of miRNAs in A. gambiae. We provided new insights on mature miRNA sequence diversity and functional shifts in the mosquito miRNA evolution. We identified a set of the differentially expressed miRNAs that respond to normal and infectious blood meals. The extended set of Anopheles miRNAs and their isoforms provides a basis for further experimental studies of miRNA expression patterns and biological functions in A. gambiae.
    Full-text · Article · Jul 2014 · BMC Genomics
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