• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Oct 1998; 150(2): 723–733.
PMCID: PMC1460370

Evidence for 3' untranslated region-dependent autoregulation of the Drosophila gene encoding the neuronal nuclear RNA-binding protein ELAV.


The Drosophila locus embryonic lethal abnormal visual system (elav) encodes a nuclear RNA-binding protein essential for normal neuronal differentiation and maintenance of neurons. ELAV is thought to play its role by binding to RNAs produced by other genes necessary for neuronal differentiation and consequently to affect their metabolism by an as yet unknown mechanism. ELAV structural homologues have been identified in a wide range of organisms, including humans, indicating an important conserved role for the protein. Analysis of elav germline transformants presented here shows that one copy of elav minigenes lacking a complete 3' untranslated region (3' UTR) rescues null mutations at elav, but that two copies are lethal. Additional in vivo experiments demonstrate that elav expression is regulated through the 3' UTR of the gene and indicate that this level of regulation is dependent upon ELAV itself. Because ELAV is an RNA-binding protein, the simplest model to account for these findings is that ELAV binds to the 3' UTR of its own RNA to autoregulate its expression. I discuss the implications of these results for normal elav function.

Full Text

The Full Text of this article is available as a PDF (207K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Abe R, Sakashita E, Yamamoto K, Sakamoto H. Two different RNA binding activities for the AU-rich element and the poly(A) sequence of the mouse neuronal protein mHuC. Nucleic Acids Res. 1996 Dec 15;24(24):4895–4901. [PMC free article] [PubMed]
  • Abe R, Yamamoto K, Sakamoto H. Target specificity of neuronal RNA-binding protein, Mel-N1: direct binding to the 3' untranslated region of its own mRNA. Nucleic Acids Res. 1996 Jun 1;24(11):2011–2016. [PMC free article] [PubMed]
  • Bashaw GJ, Baker BS. The regulation of the Drosophila msl-2 gene reveals a function for Sex-lethal in translational control. Cell. 1997 May 30;89(5):789–798. [PubMed]
  • Bier E, Ackerman L, Barbel S, Jan L, Jan YN. Identification and characterization of a neuron-specific nuclear antigen in Drosophila. Science. 1988 May 13;240(4854):913–916. [PubMed]
  • Burd CG, Dreyfuss G. Conserved structures and diversity of functions of RNA-binding proteins. Science. 1994 Jul 29;265(5172):615–621. [PubMed]
  • Campos AR, Grossman D, White K. Mutant alleles at the locus elav in Drosophila melanogaster lead to nervous system defects. A developmental-genetic analysis. J Neurogenet. 1985 Jun;2(3):197–218. [PubMed]
  • Campos AR, Rosen DR, Robinow SN, White K. Molecular analysis of the locus elav in Drosophila melanogaster: a gene whose embryonic expression is neural specific. EMBO J. 1987 Feb;6(2):425–431. [PMC free article] [PubMed]
  • Celniker SE, Lewis EB. Molecular basis of transabdominal--a sexually dimorphic mutant of the bithorax complex of Drosophila. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1566–1570. [PMC free article] [PubMed]
  • Chagnovich D, Cohn SL. Binding of a 40-kDa protein to the N-myc 3'-untranslated region correlates with enhanced N-myc expression in human neuroblastoma. J Biol Chem. 1996 Dec 27;271(52):33580–33586. [PubMed]
  • Chagnovich D, Fayos BE, Cohn SL. Differential activity of ELAV-like RNA-binding proteins in human neuroblastoma. J Biol Chem. 1996 Dec 27;271(52):33587–33591. [PubMed]
  • Chen CY, Shyu AB. AU-rich elements: characterization and importance in mRNA degradation. Trends Biochem Sci. 1995 Nov;20(11):465–470. [PubMed]
  • Chung S, Jiang L, Cheng S, Furneaux H. Purification and properties of HuD, a neuronal RNA-binding protein. J Biol Chem. 1996 May 10;271(19):11518–11524. [PubMed]
  • Chung S, Eckrich M, Perrone-Bizzozero N, Kohn DT, Furneaux H. The Elav-like proteins bind to a conserved regulatory element in the 3'-untranslated region of GAP-43 mRNA. J Biol Chem. 1997 Mar 7;272(10):6593–6598. [PubMed]
  • Ma WJ, Cheng S, Campbell C, Wright A, Furneaux H. Cloning and characterization of HuR, a ubiquitously expressed Elav-like protein. J Biol Chem. 1996 Apr 5;271(14):8144–8151. [PubMed]
  • Ma WJ, Chung S, Furneaux H. The Elav-like proteins bind to AU-rich elements and to the poly(A) tail of mRNA. Nucleic Acids Res. 1997 Sep 15;25(18):3564–3569. [PMC free article] [PubMed]
  • Curtis D, Lehmann R, Zamore PD. Translational regulation in development. Cell. 1995 Apr 21;81(2):171–178. [PubMed]
  • Dreyfuss G, Hentze M, Lamond AI. From transcript to protein. Cell. 1996 Jun 28;85(7):963–972. [PubMed]
  • Gao FB, Keene JD. Hel-N1/Hel-N2 proteins are bound to poly(A)+ mRNA in granular RNP structures and are implicated in neuronal differentiation. J Cell Sci. 1996 Mar;109(Pt 3):579–589. [PubMed]
  • Gao FB, Carson CC, Levine T, Keene JD. Selection of a subset of mRNAs from combinatorial 3' untranslated region libraries using neuronal RNA-binding protein Hel-N1. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11207–11211. [PMC free article] [PubMed]
  • Perron M, Bourlitio P, Wegnez M, Théodore L. Subcellular distribution of Xenopus XEL-1 protein, a member of the neuron-specific ELAV/Hu family, revealed by epitope tagging. DNA Cell Biol. 1997 May;16(5):579–587. [PubMed]
  • Granadino B, Penalva LO, Green MR, Valcárcel J, Sánchez L. Distinct mechanisms of splicing regulation in vivo by the Drosophila protein Sex-lethal. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7343–7348. [PMC free article] [PubMed]
  • Pirrotta V. Vectors for P-mediated transformation in Drosophila. Biotechnology. 1988;10:437–456. [PubMed]
  • Okano HJ, Darnell RB. A hierarchy of Hu RNA binding proteins in developing and adult neurons. J Neurosci. 1997 May 1;17(9):3024–3037. [PubMed]
  • Robinow S, White K. Characterization and spatial distribution of the ELAV protein during Drosophila melanogaster development. J Neurobiol. 1991 Jul;22(5):443–461. [PubMed]
  • Homyk T, Jr, Isono K, Pak WL. Developmental and physiological analysis of a conditional mutation affecting photoreceptor and optic lobe development in Drosophila melanogaster. J Neurogenet. 1985 Nov;2(5):309–324. [PubMed]
  • Robinow S, Campos AR, Yao KM, White K. The elav gene product of Drosophila, required in neurons, has three RNP consensus motifs. Science. 1988 Dec 16;242(4885):1570–1572. [PubMed]
  • Jacobson A, Peltz SW. Interrelationships of the pathways of mRNA decay and translation in eukaryotic cells. Annu Rev Biochem. 1996;65:693–739. [PubMed]
  • Jain RG, Andrews LG, McGowan KM, Pekala PH, Keene JD. Ectopic expression of Hel-N1, an RNA-binding protein, increases glucose transporter (GLUT1) expression in 3T3-L1 adipocytes. Mol Cell Biol. 1997 Feb;17(2):954–962. [PMC free article] [PubMed]
  • Sachs AB. Messenger RNA degradation in eukaryotes. Cell. 1993 Aug 13;74(3):413–421. [PubMed]
  • Sakai K, Gofuku M, Kitagawa Y, Ogasawara T, Hirose G, Yamazaki M, Koh CS, Yanagisawa N, Steinman L. A hippocampal protein associated with paraneoplastic neurologic syndrome and small cell lung carcinoma. Biochem Biophys Res Commun. 1994 Mar 30;199(3):1200–1208. [PubMed]
  • Jiménez F, Campos-Ortega JA. Genes in subdivision 1B of the Drosophila melanogaster X-chromosome and their influence on neural development. J Neurogenet. 1987 Jun;4(4):179–200. [PubMed]
  • Samson ML, Lisbin MJ, White K. Two distinct temperature-sensitive alleles at the elav locus of Drosophila are suppressed nonsense mutations of the same tryptophan codon. Genetics. 1995 Nov;141(3):1101–1111. [PMC free article] [PubMed]
  • Karess RE, Rubin GM. Analysis of P transposable element functions in Drosophila. Cell. 1984 Aug;38(1):135–146. [PubMed]
  • Kelley RL, Kuroda MI. Equality for X chromosomes. Science. 1995 Dec 8;270(5242):1607–1610. [PubMed]
  • Steller U, Kohls S, Müller B, Söller R, Müller R, Schlender J, Blohm DH. The RNA binding protein HuD: rat cDNA and analysis of the alternative spliced mRNA in neuronal differentiating cell lines P19 and PC12. Brain Res Mol Brain Res. 1996 Jan;35(1-2):285–296. [PubMed]
  • Kelley RL, Wang J, Bell L, Kuroda MI. Sex lethal controls dosage compensation in Drosophila by a non-splicing mechanism. Nature. 1997 May 8;387(6629):195–199. [PubMed]
  • Kenan DJ, Query CC, Keene JD. RNA recognition: towards identifying determinants of specificity. Trends Biochem Sci. 1991 Jun;16(6):214–220. [PubMed]
  • Szabo A, Dalmau J, Manley G, Rosenfeld M, Wong E, Henson J, Posner JB, Furneaux HM. HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. Cell. 1991 Oct 18;67(2):325–333. [PubMed]
  • Kim YJ, Baker BS. The Drosophila gene rbp9 encodes a protein that is a member of a conserved group of putative RNA binding proteins that are nervous system-specific in both flies and humans. J Neurosci. 1993 Mar;13(3):1045–1056. [PubMed]
  • Thummel CS, Boulet AM, Lipshitz HD. Vectors for Drosophila P-element-mediated transformation and tissue culture transfection. Gene. 1988 Dec 30;74(2):445–456. [PubMed]
  • Wakamatsu Y, Weston JA. Sequential expression and role of Hu RNA-binding proteins during neurogenesis. Development. 1997 Sep;124(17):3449–3460. [PubMed]
  • King PH, Levine TD, Fremeau RT, Jr, Keene JD. Mammalian homologs of Drosophila ELAV localized to a neuronal subset can bind in vitro to the 3' UTR of mRNA encoding the Id transcriptional repressor. J Neurosci. 1994 Apr;14(4):1943–1952. [PubMed]
  • Yao KM, White K. Organizational analysis of elav gene and functional analysis of ELAV protein of Drosophila melanogaster and Drosophila virilis. Mol Cell Biol. 1991 Jun;11(6):2994–3000. [PMC free article] [PubMed]
  • Koushika SP, Lisbin MJ, White K. ELAV, a Drosophila neuron-specific protein, mediates the generation of an alternatively spliced neural protein isoform. Curr Biol. 1996 Dec 1;6(12):1634–1641. [PubMed]
  • Yao KM, Samson ML, Reeves R, White K. Gene elav of Drosophila melanogaster: a prototype for neuronal-specific RNA binding protein gene family that is conserved in flies and humans. J Neurobiol. 1993 Jun;24(6):723–739. [PubMed]
  • Levine TD, Gao F, King PH, Andrews LG, Keene JD. Hel-N1: an autoimmune RNA-binding protein with specificity for 3' uridylate-rich untranslated regions of growth factor mRNAs. Mol Cell Biol. 1993 Jun;13(6):3494–3504. [PMC free article] [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...