Disease relevance of elav

• The localization of the ELAV protein was studied in all developmental stages using antibodies that were generated against a hybrid protein made in Escherichia coli [1].
• Some patients with small cell lung cancer (SCLC) or neuroblastoma develop an immune response against HuD, a human homologue of the Drosophila protein, elav, which is expressed in the nucleus and to a lesser degree the cytoplasm of neurons and tumor cells [2].

High impact information on elav

• DNA sequence data presented in this report suggest that the elav gene product is an RNA binding protein, based on the presence of RNP (ribonucleoprotein) consensus sequences [3].
• ELAV binds to erect wing (ewg) RNA 3' of a polyadenylation site in the terminal intron 6 [4].
• These data indicate that binding of 3'-end processing factors, together with ELAV, can regulate alternative splicing [4].
• Here we define a functional in vivo binding site for ELAV in neurons through the development of a reporter gene system in transgenic animals in combination with in vitro binding assays [4].
• At this polyadenylation site, ELAV inhibits 3'-end processing in vitro in a dose-dependent and sequence-specific manner, and ELAV binding is necessary in vivo to promote splicing of ewg intron 6 [4].

Biological context of elav

• Polymorphism data on para and elav (located at the middle region of the X chromosome) suggest that there is no population structure other than that caused by the X/4 fusion itself [5].
• We used RNA-binding assays and in vitro selection to identify the ELAV best binding site in the elav 3'-UTR [6].
• The long elav 3'-untranslated region (3'-UTR) is necessary for autoregulation [6].
• Finally, using transgenes we demonstrate in fly neurons that ELAV-mediated regulation of ewg intron 6 splicing requires several AU(4-6) motifs and that introduction of spacer sequence between conserved AU(4-6) motifs has a minimal effect on splicing [7].
• Since ELAV/Hu proteins preferentially bind to AU-rich regions that are generally abundant in introns and untranslated regions, it has not been clear how gene specificity is achieved [7].

Anatomical context of elav

• We found that nearly all lgl micrometastases co-express the neuronal cell marker, ELAV, and the glial cell marker, REPO [8].
• Association of the neuron-specific RNA binding domain-containing protein ELAV with the coiled body in Drosophila neurons [9].
• A DNA segment containing elav+ function was defined through germ line transformation experiments [10].
• This overall structure is remarkably similar to the structures of the Drosophila melanogaster elav gene product, the human neuronal antigen HuD, and the cytolytic lymphocyte protein TIA-1 [11].
• In contrast, we found that cells located at the margins of the cortex and the neuropil, and within the neuropil, as well as smaller cortical cells found throughout the brain's cortex, were elav negative, supporting the notion that they are glial in nature [12].

Associations of elav with chemical compounds

• Two distinct temperature-sensitive alleles at the elav locus of Drosophila are suppressed nonsense mutations of the same tryptophan codon [13].
• Similar to D. melanogaster ELAV protein, it contains three tandem RNA-binding domains and an alanine/glutamine-rich amino-terminal region [14].
• Furthermore, a D. melanogaster ORF encoding an ELAV protein with a 40-amino-acid deletion within the alanine/glutamine-rich region was also able to supply elav function in vivo [14].

Physical interactions of elav

• Here we used a combination of in vitro biochemical experiments together with phylogenetic comparisons and in vivo analysis of Drosophila transgenes to study ELAV binding to the last ewg intron and splicing regulation [7].
• Two putative Cpo proteins contain similar but nonidentical RNA-binding domains that are most homologous to the RNA-binding domains of the Drosophila embryonic lethal abnormal vision (elav) gene and a human brain protein that has been implicated in a paraneoplastic sensory neuropathy [15].

Regulatory relationships of elav

• The data presented in this paper are consistent with a mechanism in which ELAV increases the splicing efficiency of ewg transcripts in alternatively spliced regions rather than with a mechanism in which stability of specific splice forms is enhanced by ELAV [16].
• The neuron-specific RNA-binding protein ELAV regulates neuroglian alternative splicing in neurons and binds directly to its pre-mRNA [17].

Other interactions of elav

• Inferences on the evolutionary history of the Drosophila americana polymorphic X/4 fusion from patterns of polymorphism at the X-linked paralytic and elav genes [5].
• These observations provide a molecular basis for the in vivo interactions reported previously between elav and fne [6].
• In the nerve cord of elav mutant embryos, comm mRNA expression is strongly reduced in neurons, but not in midline glial cells [18].
• Equator-outwards progression of elav expression and expression of the nemo gene in the morphogenetic furrow are regulated by frizzled, which itself is dynamically expressed about the morphogenetic furrow [19].
• Drosophila arginase is produced from a nonvital gene that contains the elav locus within its third intron [20].

Analytical, diagnostic and therapeutic context of elav

• Further, sizing of the ELAV-RNA complex and a series of titration experiments indicate that ELAV forms a dodecameric complex on 135 nucleotides in the last ewg intron [7].
• The subcellular distribution of the Drosophila nervous system-specific RNA binding domain-containing protein ELAV was investigated using ELAV-specific antibodies and scanning confocal laser microscopy [9].
• In situ hybridization experiments clearly demonstrate that the embryonic expression of elav is restricted to the nervous system [10].
• The embryonic lethal abnormal visual system (elav) locus in Drosophila melanogaster, a vital gene mapping within the 1B5-1B9 region of the X-chromosome has been cloned and analysed [10].

References