scholarly journals Shaping the Innate Immune Response Through Post-Transcriptional Regulation of Gene Expression Mediated by RNA-Binding Proteins

2022 ◽  
Vol 12 ◽  
Author(s):  
Anissa Guillemin ◽  
Anuj Kumar ◽  
Mélanie Wencker ◽  
Emiliano P. Ricci
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Transcriptional Control ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Innate Immune ◽  
Control Of Gene Expression ◽  
Expression Program

Innate immunity is the frontline of defense against infections and tissue damage. It is a fast and semi-specific response involving a myriad of processes essential for protecting the organism. These reactions promote the clearance of danger by activating, among others, an inflammatory response, the complement cascade and by recruiting the adaptive immunity. Any disequilibrium in this functional balance can lead to either inflammation-mediated tissue damage or defense inefficiency. A dynamic and coordinated gene expression program lies at the heart of the innate immune response. This expression program varies depending on the cell-type and the specific danger signal encountered by the cell and involves multiple layers of regulation. While these are achieved mainly via transcriptional control of gene expression, numerous post-transcriptional regulatory pathways involving RNA-binding proteins (RBPs) and other effectors play a critical role in its fine-tuning. Alternative splicing, translational control and mRNA stability have been shown to be tightly regulated during the innate immune response and participate in modulating gene expression in a global or gene specific manner. More recently, microRNAs assisting RBPs and post-transcriptional modification of RNA bases are also emerging as essential players of the innate immune process. In this review, we highlight the numerous roles played by specific RNA-binding effectors in mediating post-transcriptional control of gene expression to shape innate immunity.

scholarly journals Gene expression variability across cells and species shapes innate immunity

2017 ◽  
Author(s):  
Tzachi Hagai ◽  
Xi Chen ◽  
Ricardo J Miragaia ◽  
Tomás Gomes ◽  
Raghd Rostom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Innate Immune ◽  
First Line ◽  
Expression Variability ◽  
Cytokines And Chemokines ◽  
Cell To Cell Variability ◽  
Unique Expression Pattern

SummaryAs the first line of defence against pathogens, cells mount an innate immune response, which is highly variable from cell to cell. The response must be potent yet carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here, we characterise this programme’s transcriptional divergence between species and expression variability across cells. Using bulk and single-cell transcriptomics in primate and rodent fibroblasts challenged with an immune stimulus, we reveal a striking architecture of the innate immune response. Rapidly diverging genes, including cytokines and chemokines, also vary across cells and have distinct promoter structures. Conversely, genes involved in response regulation, such as transcription factors and kinases, are conserved between species and display low cell-to-cell variability. We suggest that this unique expression pattern, observed across species and conditions, has evolved as a mechanism for fine-tuned regulation, to achieve an effective but balanced response.

Regulation of B-cell differentiation by microRNAs and RNA-binding proteins

2008 ◽  
Vol 36 (6) ◽  
pp. 1191-1193 ◽  
Author(s):  
Alexander Ademokun ◽  
Martin Turner
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Transcriptional Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
B Cell Differentiation ◽  
Control Of Gene Expression ◽  
Gm Csf ◽  
Factor Α

Post-transcriptional control of gene expression is an important mechanism for maintaining cellular homoeostasis and regulating the immune response to infection. It allows control of mRNA abundance, translation and localization. Mechanisms for post-transcriptional control involve RNA-binding proteins and miRNAs (microRNAs). The TTP(tristetraprolin) family of proteins recognize and bind AU-rich elements. Deletion of TTP led to a systemic autoimmune syndrome with excess circulating TNFα (tumour necrosis factor α) and GM-CSF (granulocyte/macrophage colony-stimulating factor) due to aberrantly stabilized mRNA. The family may also have a role in control of lymphocyte development and function. miRNAs regulate gene expression by promoting decay or inhibiting translation of transcripts with base pair complementarity. The importance of miRNAs in lymphocytes is highlighted by the T-cell-specific deletion of Dicer, an enzyme required for miRNA-mediated processing and from the phenotype of bic (B-cell integration cluster)/miR-155 (miRNA 155)-deficient mice.

scholarly journals Auto-regulatory feedback by RNA-binding proteins

2019 ◽  
Vol 11 (10) ◽  
pp. 930-939 ◽  
Author(s):  
Michaela Müller-McNicoll ◽  
Oliver Rossbach ◽  
Jingyi Hui ◽  
Jan Medenbach
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Transcriptional Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Feedback Regulation ◽  
Control Of Gene Expression ◽  
Cell Fate Decisions

Abstract RNA-binding proteins (RBPs) are key regulators in post-transcriptional control of gene expression. Mutations that alter their activity or abundance have been implicated in numerous diseases such as neurodegenerative disorders and various types of cancer. This highlights the importance of RBP proteostasis and the necessity to tightly control the expression levels and activities of RBPs. In many cases, RBPs engage in an auto-regulatory feedback by directly binding to and influencing the fate of their own mRNAs, exerting control over their own expression. For this feedback control, RBPs employ a variety of mechanisms operating at all levels of post-transcriptional regulation of gene expression. Here we review RBP-mediated autogenous feedback regulation that either serves to maintain protein abundance within a physiological range (by negative feedback) or generates binary, genetic on/off switches important for e.g. cell fate decisions (by positive feedback).

scholarly journals Compendium of Methods to Uncover RNA-Protein Interactions In Vivo

2021 ◽  
Vol 4 (1) ◽  
pp. 22
Author(s):  
Mrinmoyee Majumder ◽  
Viswanathan Palanisamy
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Patterns ◽  
Control Of Gene Expression ◽  
Regulatory Pathways ◽  
Advantages And Disadvantages ◽  
Protein Nucleic Acid

Control of gene expression is critical in shaping the pro-and eukaryotic organisms’ genotype and phenotype. The gene expression regulatory pathways solely rely on protein–protein and protein–nucleic acid interactions, which determine the fate of the nucleic acids. RNA–protein interactions play a significant role in co- and post-transcriptional regulation to control gene expression. RNA-binding proteins (RBPs) are a diverse group of macromolecules that bind to RNA and play an essential role in RNA biology by regulating pre-mRNA processing, maturation, nuclear transport, stability, and translation. Hence, the studies aimed at investigating RNA–protein interactions are essential to advance our knowledge in gene expression patterns associated with health and disease. Here we discuss the long-established and current technologies that are widely used to study RNA–protein interactions in vivo. We also present the advantages and disadvantages of each method discussed in the review.

TLR2-mediated innate immune priming boosts lung anti-viral immunity

2020 ◽  
pp. 2001584
Author(s):  
Jason Girkin ◽  
Su-Ling Loo ◽  
Camille Esneau ◽  
Steven Maltby ◽  
Francesca Mercuri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immunity ◽  
Viral Load ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Immune Priming ◽  
Tlr2 Activation

Research questionAssessment of whether TLR2 activation boosts the innate immune response to rhinovirus infection, as a treatment strategy for virus-induced respiratory diseases.MethodsWe employed treatment with a novel TLR2 agonist (INNA-X) prior to rhinovirus infection in mice, and INNA-X treatment in differentiated human bronchial epithelial cells derived from asthmatic-donors. We assessed viral load, immune cell recruitment, cytokines, type I and III IFN production, as well as the lung tissue and epithelial cell immune transcriptome.ResultsWe show in vivo, that a single INNA-X treatment induced innate immune priming characterised by low-level IFN-λ, Fas ligand, chemokine expression and airway lymphocyte recruitment. Treatment 7-days before infection significantly reduced lung viral load, increased IFN-β/λ expression and inhibited neutrophilic inflammation. Corticosteroid treatment enhanced the anti-inflammatory effects of INNA-X. Treatment 1-day before infection increased expression of 190 lung tissue immune genes. This tissue gene expression signature was absent with INNA-X treatment 7-days before infection, suggesting an alternate mechanism, potentially via establishment of immune cell-mediated mucosal innate immunity. In vitro, INNA-X treatment induced a priming response defined by upregulated IFN-λ, chemokine and anti-microbial gene expression that preceded an accelerated response to infection enriched for NF-κB-regulated genes and reduced viral loads, even in epithelial cells derived from asthmatic donors with intrinsic delayed anti-viral immune response.ConclusionAirway epithelial cell TLR2 activation induces prolonged innate immune priming, defined by early NF-κB activation, IFN-λ expression and lymphocyte recruitment. This response enhanced anti-viral innate immunity and reduced virus-induced airway inflammation.

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