Disease relevance of Elavl1

• These results define iNOS and HuR as critical players in cytokine-induced cachexia, establishing them as potential therapeutic targets [1].
• HuR, an RNA-binding protein that regulates both the stability and cellular movement of ARE-containing mRNAs, interacts and stabilizes the p21cip1 message under UV stress in human RKO colorectal carcinoma cells [2].
• We sought to identify collections of HuR-regulated mRNAs in colon cancer cells by systematic, cDNA array-based assessment of gene expression in three systems of varying complexity [3].
• The human neuroblastoma apoptosis-related RNA-binding protein NAPOR is an ELAV-like RNA-binding protein with three characteristic RNA recognition motifs (RRMs) [4].

High impact information on Elavl1

• By using a model system of ARE dysfunction, we demonstrate that HuR does not alter the accumulation of target mRNAs in the absence of the destabilizing functions of Tristetraprolin but synergizes with the translational silencer TIA-1 to reduce the translation of cytokine mRNAs [5].
• HuR is an RNA binding protein with an alleged role in the posttranscriptional activation of inflammatory mRNAs bearing AU-rich elements (AREs) [5].
• In macrophages, HuR overexpression induced the translational silencing of specific cytokine mRNAs despite positive or nominal effects on their corresponding turnover [5].
• We found that, in hepatocytes, AICAR increases HuR binding to cyclin A2 messenger RNA (mRNA) as well as the expression and stability of this mRNA and that SAM blocks these events [6].
• S-adenosylmethionine regulates cytoplasmic HuR via AMP-activated kinase [6].

Biological context of Elavl1

• mHuA (Elavl1) belongs to a highly conserved family of genes encoding RNA-binding proteins and has been linked to cell growth and proliferation through its regulation of mRNA stability [7].
• Analysis of the 5' end of the mouse Elavl1 (mHuA) gene reveals a transcriptional regulatory element and evidence for conserved genomic organization [7].
• The down-regulation of HuR expression mediated through small interfering RNA further confirmed the role of HuR in the regulation of AChE mRNA levels [8].
• These data suggest that the Hua-Hud genes arose from gene duplication and dispersion, while the other genes are dispersed in the genome [9].
• Down-regulation of HuR expression by RNA interference prevented the chronic ethanol-induced increase in expression of luciferase reporters containing the TNFalpha 3'-UTR [10].

Anatomical context of Elavl1

• The RNA-binding protein HuR binds to acetylcholinesterase transcripts and regulates their expression in differentiating skeletal muscle cells [8].
• ELAV protein HuA (HuR) can redistribute between nucleus and cytoplasm and is upregulated during serum stimulation and T cell activation [11].
• After chronic ethanol feeding, HuR quantity in the cytosol was greater, both at baseline and in response to LPS, compared with pair-fed controls [10].
• Chronic ethanol exposure increases the binding of HuR to the TNFalpha 3'-untranslated region in macrophages [10].
• In Kupffer cells, HuR was primarily localized to the nucleus and then translocated to the cytosol in response to LPS in both pair- and ethanol-fed rats [10].

Associations of Elavl1 with chemical compounds

• More importantly, reduction of HuR levels by small interfering RNA inhibited apigenin-mediated stabilization of COX-2 mRNA [12].
• A HeLa cell tetracycline-regulated reporter system was used to determine the effect of HuR on mRNA stability [13].
• A series of experiments, using cell culture models or in vitro assays, has shown that the RNA-binding protein HuR increases the half-life of some messenger RNAs that contain adenylate/uridylate-rich decay elements [14].
• In polyribosomes from female mouse SMG, HuR levels doubled after 6 h of DHT, but decreased by 80% after 24- and 48-h DHT treatment [15].

Physical interactions of Elavl1

• After chronic ethanol feeding, HuR binding to the TNFalpha A + U-rich element was increased by more than 5-fold at baseline and in response to LPS, compared with pair-fed controls [10].
• We tested if HuR binds the interleukin-2 mRNA and whether such binding is related to CD28-mediated stabilization of the mRNA [16].
• RhoB mRNA is stabilized by HuR after UV light [17].
• Interrupting the TRN2-HuR complex using RNA interference against TRN2, or the cell-permeable peptides (AP) fused to the HuR nucleocytoplasmic shuttling domain (HNS), enhanced the efficiency of myofiber formation [18].

Regulatory relationships of Elavl1

• Moreover, we show that HuR regulates iNOS expression in an AMP-activated protein kinase (AMPK)-dependent manner [1].

Other interactions of Elavl1

• NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release [1].
• Finally, we compared AUF1 and HuR expression with accumulation of one common target mRNA, c-myc [19].
• The neuron-specific ELAV-like HuB, HuC, and HuD RNA-binding proteins act posttranscriptionally by binding to adenine- and uridine-rich elements (AREs) in the 3' untranslated region of a set of target mRNAs, and by increasing mRNA cytoplasmic stability and/or rate of translation [20].
• Binding of HuR to the mouse interleukin-2 mRNA has not been studied [16].
• Therefore, we propose a model in which UVL induces stress-activated signal transduction leading to nuclear/cytoplasmic shuttling of HuR and subsequent stabilization of RhoB mRNA [17].

Analytical, diagnostic and therapeutic context of Elavl1

• Using several complementary approaches including supershift REMSA, mRNA-binding protein pull-down assays, and immunoprecipitation followed by reverse transcription-PCR, we found that the mRNA-stabilizing protein HuR interacts directly with AChE transcripts [8].
• In EMSAs both complexes were supershifted by an anti-HuR antibody, while Western blotting also demonstrated the presence of HuR in the P100 extract [13].
• In vitro mobility shift assays demonstrated that HuR bound the 3'-UTR of RhoB at three distinct locations (nucleotides 1342-1696, 1765-1920 and 1897-1977) suggesting a regulatory role for this RNA-binding protein [17].
• However, no upregulation of HuR or AUF1 accompanies the upregulation of c-myc mRNA following partial hepatectomy [21].
• HuR immunoprecipitations were positive for RhoB mRNA indicating an in vivo association, and Western blot analysis and immunofluorescence demonstrated that HuR rapidly partitions from the nucleus to the cytoplasm after UVL [17].

References