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

Abstract

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.

CircCUX1 Promotes Colorectal Cancer Progression by the microRNA 500a-3p/MUC4/β-catenin/C-MYC Axis and Is Regulated by ELAVL1

“…ELAVL1 stabilizes mRNA by binding to the 3'UTR region of mRNA . [36,37]. In this study, ELAVL1 was found to be a potential RBP of circCUX1 through several databases.…”

CMLD-2 Attenuates Myofibroblast Activation and Bleomycin-Induced Pulmonary Fibrosis in Mice through Antagonizing ELAVL1-Mediated Osteopontin mRNA Stabilization

“…Our study compared the HuR-binding RNA profiles between naïve fibroblasts and TGF-β1-treated fibroblasts; CLIP-seq and RNA half-life data presented here various differently regulated genes covering inflammatory and various cellular processes; the possibly anti-inflammatory effect of CMLD-2 is suggested by its protection from bleomycin-induced early pulmonary injury at day 14. Other previous studies have revealed other downstream genes regulated by HuR in cancers or in fibrotic models, such as proinflammatory genes 42,43 , Snail1 33 and TGF-β1 32,44 . As pulmonary fibrosis is a sophisticated process involving numbers of molecular cell biological mechanisms 6 , we propose that the universal profibrotic and proinflammatory properties of HuR may justify it as a promising target for fibrosis.…”

The interplay between lncRNAs, RNA-binding proteins and viral genome during SARS-CoV-2 infection reveals strong connections with regulatory events involved in RNA metabolism and immune response

“…This connection map includes information about the specific RBPs interacting with the upregulated lncRNAs together with the density of RBP-binding sites in each lncRNA determined by CLIP experiments and extracted from the ENCORI database [42]. Considering the global number of RNA-binding sites determined by CLIP experiments, the most represented RBPs comprised the EIF4A3 helicase, core of the exon-junction complex [58], the FUS transcriptional regulator involved in DNA repair, transcription and splicing [59], the TAF15 transcriptional regulator [60], the ELAVL1 regulator of RNA stability [61], and the IGF2BP2 protein, a previously known regulatory player that can interact with several ncRNAs including miRNAs and lncRNAs [62]. Additional overrepresented RBPs include splicing factors U2AF2, FBL and CSTF2T, and the nucleolar proteins NOP56 and NOP58.…”