Reactome | HuR (ELAVL1) binds and stabilizes mRNA

HuR (ELAVL1) binds and stabilizes mRNA

Stable Identifier

R-HSA-450520

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, nucleoplasm

ReviewStatus

5/5

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HuR (ELAVL1) is a ubiquitous protein that binds AU-rich elements in mRNAs and acts to stabilize the mRNAs. HuR activity is controlled by phosphorylation, with PKC alpha and PCK delta enhancing the ability of HuR to bind and stabilize mRNAs. Binding of mRNAs occurs in the nucleus and HuR then interacts with the CRM1 export pathway to transfer the mRNA to the cytoplasm. The mechanism by which HuR shields the mRNA from degradation is unknown.
HuR also regulates translation of some mRNAs, in some cases repressing translation and in some cases enhancing translation of bound mRNAs by recruiting them to polysomes.
HuR binds and regulates mRNAs encoding Cyclooxygenase-2 (COX2, PTGS2), Cyclin A (CCNA, CCNA2), Cyclin D1 (CCND1), Cyclin B1 (CCNB1), CD83 antigen (CD83), and proto-oncogene c-Fos (FOS).
HuR is a member of a family of proteins that also contains HuD (ELAVL4), HuB (ELAVL2), and HuC (ELAVL3). HuB, HuC, and HuD are specifically expressed in neural tissue.
HuR participates in apoptosis. During lethal stress HuR becomes mostly cytoplasmic and is a target of Caspase-3 and Caspase-7. The cleavage products of HuR in turn promote apoptosis.

Literature References

PubMed ID	Title	Journal	Year
16391004	AU-rich elements and associated factors: are there unifying principles? Barreau, C, Paillard, L, Osborne, HB	Nucleic Acids Res	2005
18285462	Posttranslational modification of the AU-rich element binding protein HuR by protein kinase Cdelta elicits angiotensin II-induced stabilization and nuclear export of cyclooxygenase 2 mRNA Pfeilschifter, J, Müller, R, Doller, A, Huwiler, A, Akool, el-S, Eberhardt, W, Radeke, HH	Mol Cell Biol	2008
14976220	Roles of AUF1 isoforms, HuR and BRF1 in ARE-dependent mRNA turnover studied by RNA interference Certa, U, Gross, B, Wegmueller, D, Raineri, I, Moroni, C	Nucleic Acids Res	2004
12704645	Post-transcriptional regulation of gene expression by degradation of messenger RNAs Ceriani, MC, Bevilacqua, A, Capaccioli, S, Nicolin, A	J Cell Physiol	2003
12440953	AU-rich element-mediated translational control: complexity and multiple activities of trans-activating factors Kruys, V, Zhang, T, Huez, G, Gueydan, C	Biochem Soc Trans	2002
17392515	Protein kinase C alpha-dependent phosphorylation of the mRNA-stabilizing factor HuR: implications for posttranscriptional regulation of cyclooxygenase-2 Pfeilschifter, J, Müller, R, Doller, A, Huwiler, A, Eberhardt, W, Radeke, HH	Mol Biol Cell	2007