• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of narLink to Publisher's site
Nucleic Acids Res. Jun 15, 1998; 26(12): 2989–2994.
PMCID: PMC147648

Down regulation of extramacrochaetae mRNA by a Drosophila neural RNA binding protein Rbp9 which is homologous to human Hu proteins.


Rbp9 is an RNA binding protein expressed mainly in the central nervous system of adult Drosophilamelanogaster. Rbp9 shares a high degree of sequence similarity with human neural proteins referred to as Hu antigens. Hu antigens bind to U-rich mRNA destabilizing elements with a high affinity and, thus, have been implicated as regulators of mRNA stability. Using in vitro RNA binding assays, we found that Rbp9 binds strongly to poly U sequences. We then employed a Selex system to identify a consensus Rbp9 binding site (UUUXUUUU). Information obtained from the Selex results allowed the detection of two repeats of the Rbp9 consensus binding sequence in the 3' untranslated region of extramacrochaetae mRNA. UV crosslinking experiments demonstrated that Rbp9 interactsspecifically with emc mRNA. The requirement of Rbp9 protein in the down regulation of emc mRNA was confirmed by northern (RNA) analysis, which revealed that the level of emc mRNA increased 10-fold in rbp9 mutant flies. Taken together with the in vitro RNA binding results, the genetic evidence obtained strongly supports the hypothesis that Rbp9 functions as a regulator of RNA stability.

Full Text

The Full Text of this article is available as a PDF (136K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bopp D, Horabin JI, Lersch RA, Cline TW, Schedl P. Expression of the Sex-lethal gene is controlled at multiple levels during Drosophila oogenesis. Development. 1993 Jul;118(3):797–812. [PubMed]
  • Belote JM. The control of sexual development in Drosophila melanogaster: genetic and molecular analysis of a genetic regulatory hierarchy--a minireview. Gene. 1989 Oct 15;82(1):161–167. [PubMed]
  • Birman S, Morgan B, Anzivino M, Hirsh J. A novel and major isoform of tyrosine hydroxylase in Drosophila is generated by alternative RNA processing. J Biol Chem. 1994 Oct 21;269(42):26559–26567. [PubMed]
  • Zarkower D, Hodgkin J. Molecular analysis of the C. elegans sex-determining gene tra-1: a gene encoding two zinc finger proteins. Cell. 1992 Jul 24;70(2):237–249. [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]
  • 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]
  • Good PJ. A conserved family of elav-like genes in vertebrates. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4557–4561. [PMC free article] [PubMed]
  • Wu L, Good PJ, Richter JD. The 36-kilodalton embryonic-type cytoplasmic polyadenylation element-binding protein in Xenopus laevis is ElrA, a member of the ELAV family of RNA-binding proteins. Mol Cell Biol. 1997 Nov;17(11):6402–6409. [PMC free article] [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]
  • 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]
  • 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]
  • 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]
  • 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]
  • Liu J, Dalmau J, Szabo A, Rosenfeld M, Huber J, Furneaux H. Paraneoplastic encephalomyelitis antigens bind to the AU-rich elements of mRNA. Neurology. 1995 Mar;45(3 Pt 1):544–550. [PubMed]
  • Myer VE, Fan XC, Steitz JA. Identification of HuR as a protein implicated in AUUUA-mediated mRNA decay. EMBO J. 1997 Apr 15;16(8):2130–2139. [PMC free article] [PubMed]
  • Tsai DE, Harper DS, Keene JD. U1-snRNP-A protein selects a ten nucleotide consensus sequence from a degenerate RNA pool presented in various structural contexts. Nucleic Acids Res. 1991 Sep 25;19(18):4931–4936. [PMC free article] [PubMed]
  • Cubas P, Modolell J, Ruiz-Gómez M. The helix-loop-helix extramacrochaetae protein is required for proper specification of many cell types in the Drosophila embryo. Development. 1994 Sep;120(9):2555–2566. [PubMed]
  • Kim-Ha J, Kerr K, Macdonald PM. Translational regulation of oskar mRNA by bruno, an ovarian RNA-binding protein, is essential. Cell. 1995 May 5;81(3):403–412. [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]
  • 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]
  • Hoshijima K, Kohyama A, Watakabe I, Inoue K, Sakamoto H, Shimura Y. Transcriptional regulation of the Sex-lethal gene by helix-loop-helix proteins. Nucleic Acids Res. 1995 Sep 11;23(17):3441–3448. [PMC free article] [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]
  • Inoue K, Hoshijima K, Sakamoto H, Shimura Y. Binding of the Drosophila sex-lethal gene product to the alternative splice site of transformer primary transcript. Nature. 1990 Mar 29;344(6265):461–463. [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]
  • Nagoshi RN, McKeown M, Burtis KC, Belote JM, Baker BS. The control of alternative splicing at genes regulating sexual differentiation in D. melanogaster. Cell. 1988 Apr 22;53(2):229–236. [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]
  • Wang J, Dong Z, Bell LR. Sex-lethal interactions with protein and RNA. Roles of glycine-rich and RNA binding domains. J Biol Chem. 1997 Aug 29;272(35):22227–22235. [PubMed]
  • Kelley RL, Solovyeva I, Lyman LM, Richman R, Solovyev V, Kuroda MI. Expression of msl-2 causes assembly of dosage compensation regulators on the X chromosomes and female lethality in Drosophila. Cell. 1995 Jun 16;81(6):867–877. [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press


Related citations in PubMed

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...