ELAVL1 (ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R))

2008-09-01   Virginie Dormoy-Raclet , Imed-Eddine Gallouzi 

Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada

Identity

HGNC
LOCATION
19p13.2
LOCUSID
ALIAS
ELAV1,HUR,Hua,MelG
FUSION GENES

DNA/RNA

Atlas Image

Description

The ELAV1 gene, located on the minus strand, encompasses 47072 bp with 6 exons and 5 introns.

Transcription

mRNA of 2,3 kb but a second putative poly(A) signal is described leading to a 6 kb mRNA.
Coding sequence from 168 to 1148 b.

Proteins

Atlas Image

Description

The HuR protein consists of 326 aa (36 kDa). HuR has three highly conserved motifs belonging to the RNA recognition motif (RRM) superfamily and a hinge region between RRMs 2 and 3 named the HuR nucleocytoplasmic shuttling (HNS) domain. It has been shown that the HNS domain regulates the localization of HuR by mediating its association with adaptor proteins for nuclear export such as pp32/PHAP-I and APRIL and with import factors transportin-1, transportin-2, and importin.

Expression

Ubiquitously expressed

Localisation

Predominantly nuclear but shuttles between the nuclear and the cytoplasm.

Function

HuR belongs to the ELAV/Hu family (embryonic lethal abnormal vision phenotype in flies) of RNA-binding proteins (RBPs). Like other Hu/ELAVL RBPs, HuR contains 3 RRM through which it binds to specific mRNA and influences their post-transcriptional expression. HuR exhibits a high affinity for adenosine and uracil- (AU-) rich elements (ARE) leading to the stabilization and/or transport of its target host messages. In addition to its role as an mRNA stabilizer and transporter, HuR has been shown to mediate the translation of mRNAs and rarely to repress translation. Moreover, HuR plays a key role in the enhancement of caspase-dependent apoptosis induced by extreme stress conditions. In response to a lethal stress, HuR accumulates in the cytoplasm, where it undergoes caspase-mediated cleavage. This cleavage appears to be important for pp32/PHAP-I - mediated enhancement of the caspase-dependent apoptosis. HuR was shown to play others critical functions in cells responding to immune stimuli, nutrient availability, and exposure to damaging agents. Similarly, it has an important regulatory function in the progression of cells through the division cycle, the implementation of differentiation programs, the promotion of cell migration, cell invasion and a malignant phenotype, and the inhibition of replicative senescence.

Mutations

Note

No HuR mutations have been found in cancer or other diseases.

Implicated in

Entity name
Cancer
Oncogenesis
Breast , Lung , Colon and Ovary cancer. Expression of HuR is increased in all cancer tissues compared to the normal-tissue counterparts. It exists a consistent correlation between HuR expression levels and advancing stages of malignancy.
Entity name
Cachexia
Disease
Cachexia, characterized by the excessive loss of skeletal muscle, is frequently seen in patients with chronic diseases such as cancer. The bioactive gas nitric oxide has been identified as an important player in cancer-induced cachexia because NO is directly involved in the loss of MyoD mRNA (a key factor needed for the myogenic process, which is destabilized during cachexia) and muscle fiber. These events are mediated by the ability of HuR to associate and stabilizes the message encoding the inducible NO synthase enzyme.
Entity name
Hypertension
Disease
Chronic hypertension is associated with functional and morphological alterations of the vessel wall (ie, dysfunctional vascular endothelium and thickening of the smooth muscle layer). The pathomechanisms accounting for hypertension-induced vascular alterations are likely to be multifactorial. HuR is not only an important factor controlling vascular gene expression, but it is also subject to control by vasoactive factors that regulate cGMP and cAMP levels and downregulate its expression.
Entity name
Paraneoplastic neurological disease
Disease
Paraneoplastic enecephalomyelitis/sensory neuronopathy (PEM/SSN) is characterized by the presence of a common autoantibody, referred to as anti-Hu or type I anti-neuronal nuclear antibody (ANNA-1). The target of these antibodies is the family of Hu antigens (Hel-N1, HuC, HuD and HuR).

Bibliography

Pubmed IDLast YearTitleAuthors
112893082001HuR and mRNA stability.Brennan CM et al
160247902005NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release.Di Marco S et al
175484722007The RNA-binding protein HuR promotes cell migration and cell invasion by stabilizing the beta-actin mRNA in a U-rich-element-dependent manner.Dormoy-Raclet V et al
96288801998Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs.Fan XC et al
105857601999Hu antigen specificities of ANNA-I autoantibodies in paraneoplastic neurological disease.King PH et al
158832322005Human-antigen R (HuR) expression in hypertension: downregulation of the mRNA stabilizing protein HuR in genetic hypertension.Klöss S et al
171329322005HuR: post-transcriptional paths to malignancy.López de Silanes I et al
181803672008Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis.Mazroui R et al
129443972003RNAi-mediated HuR depletion leads to the inhibition of muscle cell differentiation.van der Giessen K et al

Other Information

Locus ID:

NCBI: 1994
MIM: 603466
HGNC: 3312
Ensembl: ENSG00000066044

Variants:

dbSNP: 1994
ClinVar: 1994
TCGA: ENSG00000066044
COSMIC: ELAVL1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000066044ENST00000407627Q15717
ENSG00000066044ENST00000593807M0QZR9
ENSG00000066044ENST00000596154M0R055
ENSG00000066044ENST00000596459Q15717

Expression (GTEx)

0
10
20
30
40
50
60

Pathways

PathwaySourceExternal ID
AMPK signaling pathwayKEGGhsa04152
AMPK signaling pathwayKEGGko04152
Gene ExpressionREACTOMER-HSA-74160
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
mRNA SplicingREACTOMER-HSA-72172
mRNA Splicing - Major PathwayREACTOMER-HSA-72163
Regulation of mRNA stability by proteins that bind AU-rich elementsREACTOMER-HSA-450531
HuR (ELAVL1) binds and stabilizes mRNAREACTOMER-HSA-450520
IL-17 signaling pathwayKEGGko04657
IL-17 signaling pathwayKEGGhsa04657

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
217231702011Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.297
217231712011Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR.271
195742982009HuR recruits let-7/RISC to repress c-Myc expression.253
173176272007Phosphorylation of HuR by Chk2 regulates SIRT1 expression.246
149812562004Identification of a target RNA motif for RNA-binding protein HuR.243
152572952004Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs.228
128217812003RNA-binding protein HuR enhances p53 translation in response to ultraviolet light irradiation.213
219358862010Posttranscriptional regulation of cancer traits by HuR.168
179678662008RNA-binding proteins HuR and PTB promote the translation of hypoxia-inducible factor 1alpha.128
280802042017Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1.128

Citation

Virginie Dormoy-Raclet ; Imed-Eddine Gallouzi

ELAVL1 (ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R))

Atlas Genet Cytogenet Oncol Haematol. 2008-09-01

Online version: http://atlasgeneticsoncology.org/gene/44237/elavl1-(elav-(embryonic-lethal-abnormal-vision-drosophila)-like-1-(hu-antigen-r))