Ariadne-1: A Vital Drosophila Gene Is Required in Development and Defines a New Conserved Family of RING-Finger Proteins

Corresponding author: Alberto Ferrús, Instituto Cajal (CSIC), Ave. Dr. Arce 37, Madrid 28002, Spain., aferrus{at}cajal.csic.es (E-mail)

Communicating editor: T. SCHÜPBACH

We report the identification and functional characterization of ariadne-1 (ari-1), a novel and vital Drosophila gene required for the correct differentiation of most cell types in the adult organism. Also, we identify a sequence-related gene, ari-2, and the corresponding mouse and human homologues of both genes. All these sequences define a new protein family by the Acid-rich, RING finger, B-box, RING finger, coiled-coil (ARBRCC) motif string. In Drosophila, ari-1 is expressed throughout development in all tissues. The mutant phenotypes are most noticeable in cells that undergo a large and rapid membrane deposition, such as rewiring neurons during metamorphosis, large tubular muscles during adult myogenesis, and photoreceptors. Occasional survivors of null alleles exhibit reduced life span, motor impairments, and short and thin bristles. Single substitutions at key cysteines in each RING finger cause lethality with no survivors and a drastic reduction of rough endoplasmic reticulum that can be observed in the photoreceptors of mosaic eyes. In yeast two-hybrid assays, the protein ARI-1 interacts with a novel ubiquitin-conjugating enzyme, UbcD10, whose sequence is also reported here. The N-terminal RING-finger motif is necessary and sufficient to mediate this interaction. Mouse and fly homologues of both ARI proteins and the Ubc can substitute for each other in the yeast two-hybrid assay, indicating that ARI represents a conserved novel mechanism in development. In addition to ARI homologues, the RBR signature is also found in the Parkinson-disease-related protein Parkin adjacent to an ubiquitin-like domain, suggesting that the study of this mechanism could be relevant for human pathology.

This article has been cited by other articles:

				J. Leymarie, E. Bruneaux, S. Gibot-Leclerc, and F. Corbineau Identification of transcripts potentially involved in barley seed germination and dormancy using cDNA-AFLP J. Exp. Bot., February 1, 2007; 58(3): 425 - 437. [Abstract] [Full Text] [PDF]

				N. Whitney, L. J. Pearson, R. Lunsford, L. McGill, R. H. Gomer, and D. F. Lindsey A Putative Ariadne-Like Ubiquitin Ligase Is Required for Dictyostelium discoideum Development. Eukaryot. Cell, October 1, 2006; 5(10): 1820 - 1825. [Abstract] [Full Text] [PDF]

				I. Marin, J. I. Lucas, A.-C. Gradilla, and A. Ferrus Parkin and relatives: the RBR family of ubiquitin ligases Physiol Genomics, May 19, 2004; 17(3): 253 - 263. [Abstract] [Full Text] [PDF]

				M.-C. Marin, J.-R. Rodriguez, and A. Ferrus Transcription of Drosophila Troponin I Gene Is Regulated by Two Conserved, Functionally Identical, Synergistic Elements Mol. Biol. Cell, March 1, 2004; 15(3): 1185 - 1196. [Abstract] [Full Text] [PDF]

				C. Mladek, K. Guger, and M.-T. Hauser Identification and Characterization of the ARIADNE Gene Family in Arabidopsis. A Group of Putative E3 Ligases Plant Physiology, January 1, 2003; 131(1): 27 - 40. [Abstract] [Full Text] [PDF]

				I. Marin and A. Ferrus Comparative Genomics of the RBR Family, Including the Parkinson's Disease-Related Gene Parkin and the Genes of the Ariadne Subfamily Mol. Biol. Evol., December 1, 2002; 19(12): 2039 - 2050. [Abstract] [Full Text] [PDF]

				S. E. Mohr and W. M. Gelbart Using the P{wHy} Hybrid Transposable Element to Disrupt Genes in Region 54D-55B in Drosophila melanogaster Genetics, September 1, 2002; 162(1): 165 - 176. [Abstract] [Full Text] [PDF]

				Y. Vigouroux, J. S. Jaqueth, Y. Matsuoka, O. S. Smith, W. D. Beavis, J. S. C. Smith, and J. Doebley Rate and Pattern of Mutation at Microsatellite Loci in Maize Mol. Biol. Evol., August 1, 2002; 19(8): 1251 - 1260. [Abstract] [Full Text] [PDF]

				H. C. Ardley, N. G. S. Tan, S. A. Rose, A. F. Markham, and P. A. Robinson Features of the Parkin/Ariadne-like Ubiquitin Ligase, HHARI, That Regulate Its Interaction with the Ubiquitin-conjugating Enzyme, UbcH7 J. Biol. Chem., May 25, 2001; 276(22): 19640 - 19647. [Abstract] [Full Text] [PDF]