MIREyA: a computational approach to detect miRNA-directed gene activation

Emerging studies demonstrate the ability of microRNAs (miRNAs) to activate genes via different mechanisms. Specifically, miRNAs may trigger an enhancer promoting chromatin remodelling in the enhancer region, thus activating the enhancer and its target genes. Here we present MIREyA, a pipeline developed to predict such miRNA-gene-enhancer trios based on an expression dataset which obviates the need to write custom scripts. We applied our pipeline to primary murine macrophages infected by Mycobacterium tuberculosis (HN878 strain) and detected Mir22, Mir221, Mir222, Mir155 and Mir1956, which could up-regulate genes related to immune responses. We believe that MIREyA is a useful tool for detecting putative miRNA-directed gene activation cases. MIREyA is available from: https://github.com/veania/MIREyA

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Computational approach for siRNA Based RNA Interference of ATP synthase subunit alpha coding gene of different strains of Mycobacterium tuberculosis

International Journal of Pharmaceutical Research ◽

10.31838/ijpr/2019.11.02.008 ◽

2019 ◽

Vol 11 (02) ◽

Keyword(s):

Mycobacterium Tuberculosis ◽

Rna Interference ◽

Atp Synthase ◽

Computational Approach ◽

Different Strains

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Microrna-130a Downregulates HCV Replication through an atg5-Dependent Autophagy Pathway

Cells ◽

10.3390/cells8040338 ◽

2019 ◽

Vol 8 (4) ◽

pp. 338 ◽

Cited By ~ 5

Author(s):

Xiaoqiong Duan ◽

Xiao Liu ◽

Wenting Li ◽

Jacinta A. Holmes ◽

Annie J. Kruger ◽

...

Keyword(s):

Immune Responses ◽

Binding Sites ◽

Target Gene ◽

Target Genes ◽

Pyruvate Metabolism ◽

Host Immune Responses ◽

Qrt Pcr ◽

Antiviral Genes ◽

Autophagy Pathway ◽

Host Antiviral Response

We previously identified that miR-130a downregulates HCV replication through two independent pathways: restoration of host immune responses and regulation of pyruvate metabolism. In this study, we further sought to explore host antiviral target genes regulated by miR-130a. We performed a RT² Profiler™ PCR array to identify the host antiviral genes regulated by miR-130a. The putative binding sites between miR-130a and its downregulated genes were predicted by miRanda. miR-130a and predicted target genes were over-expressed or knocked down by siRNA or CRISPR/Cas9 gRNA. Selected gene mRNAs and their proteins, together with HCV replication in JFH1 HCV-infected Huh7.5.1 cells were monitored by qRT-PCR and Western blot. We identified 32 genes that were significantly differentially expressed more than 1.5-fold following miR-130a overexpression, 28 of which were upregulated and 4 downregulated. We found that ATG5, a target gene for miR-130a, significantly upregulated HCV replication and downregulated interferon stimulated gene expression. miR-130a downregulated ATG5 expression and its conjugation complex with ATG12. ATG5 and ATG5-ATG12 complex affected interferon stimulated gene (ISG) such as MX1 and OAS3 expression and subsequently HCV replication. We concluded that miR-130a regulates host antiviral response and HCV replication through targeting ATG5 via the ATG5-dependent autophagy pathway.

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Inflammasomes inMycobacterium tuberculosis-Driven Immunity

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2017/2309478 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Sebastian Wawrocki ◽

Magdalena Druszczynska

Keyword(s):

Mycobacterium Tuberculosis ◽

Inflammatory Response ◽

Immune Responses ◽

Proinflammatory Cytokines ◽

Immune Cells ◽

Protein Complexes ◽

Inflammasome Activation ◽

Host Immune Responses ◽

Multimeric Protein

The development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

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HTLV-1 infection interferes with immune responses to Mycobacterium tuberculosis antigens

Retrovirology ◽

10.1186/1742-4690-12-s1-o24 ◽

2015 ◽

Vol 12 (S1) ◽

Author(s):

Natália B Carvalho ◽

Maria de Lourdes Bastos ◽

Yuri Neves ◽

Anselmo Souza ◽

Eduardo Martins Netto ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses

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Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0018 ◽

2013 ◽

Vol 368 (1632) ◽

pp. 20130018 ◽

Cited By ~ 67

Author(s):

Andrea I. Ramos ◽

Scott Barolo

Keyword(s):

Transcription Factor ◽

Binding Affinity ◽

Binding Sites ◽

Target Genes ◽

Gene Activation ◽

Transcriptional Response ◽

Morphogen Gradients ◽

Weak Binding ◽

Initial Hypothesis

In the era of functional genomics, the role of transcription factor (TF)–DNA binding affinity is of increasing interest: for example, it has recently been proposed that low-affinity genomic binding events, though frequent, are functionally irrelevant. Here, we investigate the role of binding site affinity in the transcriptional interpretation of Hedgehog (Hh) morphogen gradients . We noted that enhancers of several Hh-responsive Drosophila genes have low predicted affinity for Ci, the Gli family TF that transduces Hh signalling in the fly. Contrary to our initial hypothesis, improving the affinity of Ci/Gli sites in enhancers of dpp , wingless and stripe , by transplanting optimal sites from the patched gene, did not result in ectopic responses to Hh signalling. Instead, we found that these enhancers require low-affinity binding sites for normal activation in regions of relatively low signalling. When Ci/Gli sites in these enhancers were altered to improve their binding affinity, we observed patterning defects in the transcriptional response that are consistent with a switch from Ci-mediated activation to Ci-mediated repression. Synthetic transgenic reporters containing isolated Ci/Gli sites confirmed this finding in imaginal discs. We propose that the requirement for gene activation by Ci in the regions of low-to-moderate Hh signalling results in evolutionary pressure favouring weak binding sites in enhancers of certain Hh target genes.

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Effect of isoniazid preventive therapy on immune responses to mycobacterium tuberculosis: an open label randomised, controlled, exploratory study

BMC Infectious Diseases ◽

10.1186/s12879-015-1201-8 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 16

Author(s):

Irene Andia Biraro ◽

Moses Egesa ◽

Simon Kimuda ◽

Steven G. Smith ◽

Frederic Toulza ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Exploratory Study ◽

Preventive Therapy ◽

Isoniazid Preventive Therapy ◽

Open Label ◽

Randomised Controlled

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The exploitation of host autophagy and ubiquitin machinery by Mycobacterium tuberculosis in shaping immune responses and host defense during infection

Autophagy ◽

10.1080/15548627.2021.2021495 ◽

2022 ◽

pp. 1-22

Author(s):

Mohd Shariq ◽

Neha Quadir ◽

Anwar Alam ◽

Sheeba Zarin ◽

Javaid A. Sheikh ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Host Defense

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The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response

International Journal of Molecular Sciences ◽

10.3390/ijms23010525 ◽

2022 ◽

Vol 23 (1) ◽

pp. 525

Author(s):

Tarina Sharma ◽

Anwar Alam ◽

Aquib Ehtram ◽

Anshu Rani ◽

Sonam Grover ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Current Knowledge ◽

Immune Effector ◽

Host Immune Responses ◽

Intrinsically Disordered ◽

Multiple Strategies ◽

Latent Stage ◽

Immune Mediated ◽

Critical Edge

Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.

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