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Integrative regulatory mapping indicates that the RNA-binding protein HuR (ELAVL1) couples pre-mRNA processing and mRNA stability

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

OTHER RELATED OMICS DATASETS IN: PRJNA153883PRJNA141053PRJNA155207

ORGANISM(S): Homo sapiens

PROVIDER: GSE29780 | GEO | 2011/08/19

SECONDARY ACCESSION(S): PRJNA141053

REPOSITORIES: GEO

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Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.

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Integrative regulatory mapping indicates that the RNA-binding protein HuR (ELAVL1) couples pre-mRNA processing and mRNA stability [sequence data]

Project description:RNA-binding proteins coordinate the fates of multiple RNAs, but the principles underlying these global interactions remain poorly understood. We elucidated regulatory mechanisms of the RNA-binding protein HuR, by integrating data from diverse high-throughput targeting technologies, specifically PAR-CLIP, RIP-chip, and whole-transcript expression profiling. The number of binding sites per transcript, degree of HuR-association, and degree of HuR-dependent RNA stabilization were positively correlated. Pre-mRNA and mature mRNA containing both intronic and 3' UTR binding sites were more highly stabilized than transcripts with only 3' UTR or only intronic binding sites, suggesting that HuR couples pre-mRNA processing with mature mRNA stability. We also observed HuR-dependent splicing changes and substantial binding of HuR in poly-pyrimidine tracts of pre-mRNAs. Comparison of the spatial patterns surrounding HuR and miRNA binding sites provided functional evidence for HuR-dependent antagonism of proximal miRNA-mediated repression. We conclude that HuR coordinates gene expression outcomes at multiple interconnected steps of RNA processing. HuR (ELAVL1) PAR-CLIP

2011-08-19 | E-GEOD-29779 | biostudies-arrayexpress

Integrative regulatory mapping indicates that the RNA-binding protein HuR (ELAVL1) couples pre-mRNA processing and mRNA stability [sequence data]

2011-08-19 | GSE29779 | GEO

ELAVL1 primarily couples mRNA stability with the 3' UTRs of interferon-stimulated genes.

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Deletion of the mRNA stability factor <i>ELAVL1</i> (HuR) in pancreatic cancer cells disrupts the tumor microenvironment integrity.

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Stabilization of Dll1 mRNA by Elavl1/HuR in neuroepithelial cells undergoing mitosis.

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

Project description: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 naïve 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.

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HuR (ELAVL1) Stabilizes <i>SOX9</i> mRNA and Promotes Migration and Invasion in Breast Cancer Cells.

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Inherited disorders of cobalamin metabolism disrupt nucleocytoplasmic transport of mRNA through impaired methylation/phosphorylation of ELAVL1/HuR.

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Endothelial Immunosuppression in Atherosclerosis : Translational Control by Elavl1/HuR.

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