Disease relevance of Elavl4

• The expression of mRNA for the neuronal antigen HuD (Elavl4) associated with paraneoplastic encephalomyelitis and sensory neuronopathy was evaluated in the developing and adult rat nervous system [1].
• RT-PCR and in situ hybridization revealed that rodent homologues of HuD transcripts are present in P19 mouse embryo carcinoma and in PC12 rat pheochromocytoma cell lines both able to differentiate into neurons [2].
• In contrast, r-HuD transcripts were not detectable in the rat glioma cell line C6 [2].
• Cortical cells were infected with a replication-deficient HSV-1 vector containing the HuD cDNA in the sense orientation (HSV-HuD) [3].
• MATERIALS AND METHODS: We examined the sera of 64 children with neuroblastoma (16 with POM and 48 age-matched and stage-matched controls) by immunohistochemistry of rat brain and human cerebellum, and by Western blot analysis of protein extracts from human Purkinje cells, cortical neurons, neuroblastoma cell lines, and HuD [4].

High impact information on Elavl4

• Increase of the RNA-binding protein HuD and posttranscriptional up-regulation of the GAP-43 gene during spatial memory [5].
• Post-transcriptional regulation of acetylcholinesterase mRNAs in nerve growth factor-treated PC12 cells by the RNA-binding protein HuD [6].
• Furthermore, transfection of a reporter construct containing the AChE 3'-UTR showed that this 3'-UTR can increase expression of the reporter gene product in cells expressing HuD but not in cells expressing the antisense [6].
• We conclude that HuD stabilizes the GAP-43 mRNA through a mechanism that is dependent on the length of the poly(A) tail and involves changes in its affinity for the mRNA [7].
• Using a polysome-based in vitro mRNA decay assay, we found that addition of recombinant HuD protein to the system increased the half-life of full-length, capped, and polyadenylated GAP-43 mRNA and that this effect was caused in part by a decrease in the rate of deadenylation of the mRNA [7].

Biological context of Elavl4

• Here we report that overexpression of HuD protein in PC12 cells stabilizes the GAP-43 mRNA by delaying the onset of mRNA degradation and that this process depends on the size of the poly(A) tail [7].
• In conclusion, our results suggest that HuD is involved in the upregulation of GAP-43 expression observed at early stages of peripheral nerve regeneration [8].
• Given this evidence, we sought to investigate the involvement of HuD during nerve regeneration [8].
• The binding of HuD to this site is readily displaced by RNA oligonucleotides encoding other HuD binding sites [9].
• Overexpression of HuD, but not of its truncated form HuD I+II, promotes GAP-43 gene expression and neurite outgrowth in PC12 cells in the absence of nerve growth factor [10].

Anatomical context of Elavl4

• We have recently shown that overexpression of HuD in embryonic rat cortical cells accelerated the time course of normal neurite outgrowth and resulted in a twofold increase in GAP-43 mRNA levels [8].
• Increased expression and localization of the RNA-binding protein HuD and GAP-43 mRNA to cytoplasmic granules in DRG neurons during nerve regeneration [8].
• It is known that HuD protein and GAP-43 mRNA are expressed in the dorsal root ganglia (DRG) of adult rat and that GAP-43 is upregulated in DRG neurons during regeneration [8].
• In this study, we examined the expression patterns and levels of HuD and GAP-43 mRNA in DRG neurons following sciatic nerve injury using a combination of in situ hybridization, immunocytochemistry, and quantitative RT-PCR [8].
• To investigate whether this protein is involved in regulation of neuronal differentiation of rodent cells in vivo and in vitro, the cDNA of the rat homolog gene (r-HuD) was cloned, its expression was studied in rat brain and in neurogenic cell lines, and the splicing of its RNA was analyzed [2].

Associations of Elavl4 with chemical compounds

• Poly(A) tail length-dependent stabilization of GAP-43 mRNA by the RNA-binding protein HuD [7].
• Neuronal HuD gene encoding a mRNA stability regulator is transcriptionally repressed by thyroid hormone [11].
• In P19 cells a strong induction of HuD mRNA was observed after triggering neuronal differentiation by retinoic acid, whereas in PC12 cells the mRNA was present before and after nerve growth factor (NGF) induced neuronal differentiation [2].

Other interactions of Elavl4

• This stabilization was specific for GAP-43 mRNA containing the HuD binding element in the 3'-untranslated region and a poly(A) tail of at least 150 A nucleotides [7].

Analytical, diagnostic and therapeutic context of Elavl4

• Consistent with this idea, subcellular fractionation and immunoprecipitation analyses indicated that HuD is present in both the polysomal (P130) and cytosolic (S130) fraction [12].
• In rat brain r-HuD transcripts 3.7 and 4.2 kb in length were detected by Northern blot analysis [2].
• Using confocal microscopy we found that HuD immunoreactivity was associated with large cytoplasmic granules in the neuronal cell body and smaller granules in dendrites [12].
• After axotomy, HuD transcript and protein levels also decreased [13].

References