Lessons from studying the AU-rich elements in chronic inflammation and autoimmunity

Lourou, Niki; Gavriilidis, Maxim; Kontoyiannis, Dimitris L.

doi:10.1016/j.jaut.2019.102334

Cited by 14 publications

(35 citation statements)

References 146 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Altogether, our data show that immune stimulation leads to a loss of mRNA targets exclusively bound within introns, as well as the total number of intronic sites across all other transcripts – resulting in a net increase in the proportion of 3’UTR bound ELAVL1 targets. The change in intra-transcript target preference observed for ELAVL1 may be explained by its translocation to the cytoplasm as we and others have observed upon immune stimulation (Figure 2E) (Blanco et al, 2016; Grammatikakis et al, 2016; Lourou et al, 2019).…”

Section: Resultssupporting

confidence: 66%

ELAVL1 Primarily Couples mRNA Stability with the 3’UTRs of Interferon Stimulated Genes

Rothamel

Arcos

Kim

et al. 2020

Preprint

View full text Add to dashboard Cite

Upon detection of a pathogen, the innate immune system triggers signaling events leading to the transcription of mRNAs that encode for pro-inflammatory and anti-microbial effectors. RNA-binding proteins (RBPs) interact with these functionally critical mRNAs and temporally regulate their fates at the post-transcriptional level. One such RBP is ELAVL1, which is known to bind to introns and 3'UTRs. While significant progress has been made in understanding how ELAVL1 regulates mRNAs, how its target repertoire and binding affinity changes within an immunological context remains poorly understood. Here, we overlap four distinct high-throughput approaches to define its cell-type and context-dependent targets and determine its regulatory impact during immune activation. ELAVL1 overwhelmingly binds to intronic sites in a naive state, but during an innate immune response, ELAVL1 targets the 3'UTR - binding both previously and newly expressed mRNAs. We find that ELAVL1 mediates the RNA stability of genes that regulate the pathways involved in pathogen sensing and cytokine production. Our findings reveal the importance of examining RBP regulatory impact under dynamic transcriptomic events to best understand their post-transcriptional regulatory roles within specific biological circuitries.

show abstract

Section: Resultssupporting

confidence: 66%

ELAVL1 Primarily Couples mRNA Stability with the 3’UTRs of Interferon Stimulated Genes

Rothamel

Arcos

Kim

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Acute hepatic inflammation and its progression toward chronic liver injury require the synergetic action of several regulators of gene expression, including RNA-binding proteins such as AUBPs in different hepatic cell types (e.g., hepatocytes, hepatic stellate cells (HSCs), Kupfer cells, and other immune cells) [ 64 , 73 ]. Of note, the role of AUBPs in immune cell response under general pathological settings has been extensively reviewed in previous publications [ 74 , 75 ]. Particularly relevant to liver diseases, several cytokines, and other proinflammatory molecules, e.g., IL-8, IL-10, IL-6, COX2, TNFα, and GM-CSF, have been shown to harbor ARE-binding motifs in their 3’-UTR that allow rapid regulation by AUBPs [ 74 ].…”

Section: Aubps In Liver Inflammation and Fibrosismentioning

confidence: 99%

“…Among all AUBPs, TTP, HuR, and TIA1 appear to play preponderant roles in the modulation of inflammatory processes. TTP has indeed been reported to contribute to the termination of inflammatory responses, since its phosphorylation prevents the destabilization of proinflammatory-related and apoptotic genes in activated macrophages and neutrophils [ 75 ]. HuR silencing in activated T cells has been shown to impair Th17 commitment and function in a model of autoimmune encephalomyelitis, but in myeloid cells, HuR silencing potentiates inflammation by overactivating macrophages, thus indicating a dual and cell-specific role for HuR in inflammatory processes [ 74 ].…”

Section: Aubps In Liver Inflammation and Fibrosismentioning

confidence: 99%

“…In HepG2 hepatoma cells, APOBEC3B-induced HuR translocation into the cytoplasm has been reported to stabilize the mRNA of IL-6, a cytokine that regulates the balance between Th17 and Tregs cells [ 102 , 103 ]. Several studies have further highlighted the HuR-dependent modulation of T cell activation and polarization in physiological conditions and inflammatory diseases [ 75 , 104 , 105 , 106 , 107 , 108 ]. In line with such HuR-dependent regulatory mechanisms of T cell activation, destabilization of the transcription factor Gata3 and Th2-specific cytokines ( Il2 and Il13 ) has been observed in CD4+ T cells isolated from HuR knockout mice, suggesting a decreased ability of T cell for Th2 polarization after activation [ 109 ].…”

Section: Modulation Of Immune Responses By Aubps In Inflammation Amentioning

confidence: 99%

Section: Modulation Of Immune Responses By Aubps In Inflammation and mentioning

confidence: 99%

See 2 more Smart Citations

mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer

Dolicka

Sobolewski

Sousa

et al. 2020

IJMS

View full text Add to dashboard Cite

AU-rich element-binding proteins (AUBPs) represent important post-transcriptional regulators of gene expression. AUBPs can bind to the AU-rich elements present in the 3’-UTR of more than 8% of all mRNAs and are thereby able to control the stability and/or translation of numerous target mRNAs. The regulation of the stability and the translation of mRNA transcripts by AUBPs are highly complex processes that occur through multiple mechanisms depending on the cell type and the cellular context. While AUBPs have been shown to be involved in inflammatory processes and the development of various cancers, their important role and function in the development of chronic metabolic and inflammatory fatty liver diseases (FLDs), as well as in the progression of these disorders toward cancers such as hepatocellular carcinoma (HCC), has recently started to emerge. Alterations of either the expression or activity of AUBPs are indeed significantly associated with FLDs and HCC, and accumulating evidence indicates that several AUBPs are deeply involved in a significant number of cellular processes governing hepatic metabolic disorders, inflammation, fibrosis, and carcinogenesis. Herein, we discuss our current knowledge of the roles and functions of AUBPs in liver diseases and cancer. The relevance of AUBPs as potential biomarkers for different stages of FLD and HCC, or as therapeutic targets for these diseases, are also highlighted.

show abstract

Regulation and function of poised mRNAs in lymphocytes

Turner

2023

BioEssays

View full text Add to dashboard Cite

Pre-existing but untranslated or 'poised' mRNA exists as a means to rapidly induce the production of specific proteins in response to stimuli and as a safeguard to limit the actions of these proteins. The translation of poised mRNA enables immune cells to express quickly genes that enhance immune responses. The molecular mechanisms that repress the translation of poised mRNA and, upon stimulation, enable translation have yet to be elucidated. They likely reflect intrinsic properties of the mRNAs and their interactions with trans-acting factors that direct poised mRNAs away from or into the ribosome. Here, I discuss mechanisms by which this might be regulated.

show abstract

Lessons from studying the AU-rich elements in chronic inflammation and autoimmunity

Cited by 14 publications

References 146 publications

ELAVL1 Primarily Couples mRNA Stability with the 3’UTRs of Interferon Stimulated Genes

ELAVL1 Primarily Couples mRNA Stability with the 3’UTRs of Interferon Stimulated Genes

mRNA Post-Transcriptional Regulation by AU-Rich Element-Binding Proteins in Liver Inflammation and Cancer

Regulation and function of poised mRNAs in lymphocytes

Contact Info

Product

Resources

About