University of Zurich Zurich Open Repository and Archive

This article describes the characterization of a new Drosophila gene that we have called pitchoune (pit) (meaning small in Provence) because mutations in this gene produce larvae that cannot grow beyond the first instar larval stage although they can live as long as 7-10 days. All the tissues are equally affected and the perfectly shaped larvae are indistinguishable from first instar wild-type animals. Analysis of mutant somatic clones suggests a function in cell growth and proliferation, which is supported by the fact that cell proliferation is promoted by pit overexpression. Tagged-Pit, when transfected in S2 cells, localizes mainly to the nucleolus, pointing towards a possible role in ribosome biogenesis and, consequently, in protein biosynthesis. pit encodes a DEAD-box RNA helicase, a family of proteins involved in the control of RNA structure in many cellular processes and its closest homologue is a human DEAD-box RNA helicase, MrDb, whose corresponding gene transcription is directly activated by Myc-Max heterodimers (Grandori, C., Mac, J., Siëbelt, F., Ayer, D. E. and Eisenman, R. N. (1996) EMBO J. 15, 4344-4357). The patterns of expression of d-myc and pit are superimposable. Ectopic expression of myc in the nervous system drives an ectopic expression of pit in this tissue indicating that in Drosophila as well, pit is a potential target of d-Myc. These results suggest that myc might promote cell proliferation by activating genes that are required in protein biosynthesis, thus linking cell growth and cell proliferation. 3571 Development 125, 3571-3584 (1998) Printed in Great Britain © The Company of Biologists Limited 1998

[1]  M. Levine.  Dorsal-ventral patterning of the Drosophila embryo , 2008 .

[2]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[3]  O. Demakova,et al.  Dynamics of the sub-nuclear distribution of Modulo and the regulation of position-effect variegation by nucleolus in Drosophila. , 1998, Journal of cell science.

[4]  J. de la Cruz,et al.  Fal1p is an essential DEAD-box protein involved in 40S-ribosomal-subunit biogenesis in Saccharomyces cerevisiae , 1997, Molecular and cellular biology.

[5]  R. Moon,et al.  Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling , 1997, Nature.

[6]  M. Polymenis,et al.  Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast. , 1997, Genes & development.

[7]  Jeffrey D. Parvin,et al.  RNA Helicase A Mediates Association of CBP with RNA Polymerase II , 1997, Cell.

[8]  N. Perrimon,et al.  A new enhancer of position-effect variegation in Drosophila melanogaster encodes a putative RNA helicase that binds chromosomes and is regulated by the cell cycle. , 1997, Genetics.

[9]  M. Fournier,et al.  The rRNA-processing function of the yeast U14 small nucleolar RNA can be rescued by a conserved RNA helicase-like protein , 1997, Molecular and cellular biology.

[10]  D. Tollervey,et al.  Rok1p is a putative RNA helicase required for rRNA processing , 1997, Molecular and cellular biology.

[11]  J. Acharya,et al.  InsP3 Receptor Is Essential for Growth and Differentiation but Not for Vision in Drosophila , 1997, Neuron.

[12]  S. Zaffran,et al.  The held out wings (how) Drosophila gene encodes a putative RNA-binding protein involved in the control of muscular and cardiac activity. , 1997, Development.

[13]  C. Sun,et al.  Dbp3p, a putative RNA helicase in Saccharomyces cerevisiae, is required for efficient pre-rRNA processing predominantly at site A3 , 1997, Molecular and cellular biology.

[14]  P. O’Farrell,et al.  Limb morphogenesis: connections between patterning and growth , 1997, Current Biology.

[15]  R. DePinho,et al.  Drosophila Myc is oncogenic in mammalian cells and plays a role in the diminutive phenotype. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. Cerini,et al.  Evolution of the aminoacyl-tRNA synthetase family and the organization of the Drosophila glutamyl-prolyl-tRNA synthetase gene. Intron/exon structure of the gene, control of expression of the two mRNAs, selective advantage of the multienzyme complex. , 1997, European journal of biochemistry.

[17]  B. Edgar,et al.  Developmental Control of Cell Cycle Regulators: A Fly's Perspective , 1996, Science.

[18]  R. Eisenman,et al.  Myc and Max Homologs in Drosophila , 1996, Science.

[19]  M. Polymenis,et al.  An essential E box in the promoter of the gene encoding the mRNA cap-binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc , 1996, Molecular and cellular biology.

[20]  R. Eisenman,et al.  Myc‐Max heterodimers activate a DEAD box gene and interact with multiple E box‐related sites in vivo. , 1996, The EMBO journal.

[21]  J. Abelson,et al.  18S rRNA processing requires the RNA helicase-like protein Rrp3. , 1996, Nucleic acids research.

[22]  F. Collins,et al.  A human gene (DDX10) encoding a putative DEAD-box RNA helicase at 11q22-q23. , 1996, Genomics.

[23]  Y. Graba,et al.  The modifier of variegation modulo gene acts downstream of dorsoventral and HOM-C genes and is required for morphogenesis in Drosophila. , 1994, Developmental biology.

[24]  G. Thomas,et al.  Mitogenesis and protein synthesis: A role for ribosomal protein S6 phosphorylation? , 1994, BioEssays : news and reviews in molecular, cellular and developmental biology.

[25]  C. Guthrie,et al.  PRP28, a 'DEAD-box' protein, is required for the first step of mRNA splicing in vitro. , 1994, Nucleic acids research.

[26]  Y. Jan,et al.  Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. , 1994, Genes & development.

[27]  F. Fuller-Pace,et al.  RNA helicases: modulators of RNA structure. , 1994, Trends in cell biology.

[28]  P. Lasko,et al.  Localization of vasa protein to the Drosophila pole plasm is independent of its RNA-binding and helicase activities. , 1994, Development.

[29]  B. Amati,et al.  Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death. , 1994, Current opinion in genetics & development.

[30]  D. Roussell,et al.  glh-1, a germ-line putative RNA helicase from Caenorhabditis, has four zinc fingers. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[31]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[32]  G. Rubin,et al.  Analysis of genetic mosaics in developing and adult Drosophila tissues. , 1993, Development.

[33]  G. Evan,et al.  The role of c-myc in cell growth. , 1993, Current opinion in genetics & development.

[34]  R. Levis,et al.  Cell lineage‐specific expression of modulo, a dose‐dependent modifier of variegation in Drosophila. , 1992, The EMBO journal.

[35]  J. Woolford,et al.  A putative ATP-dependent RNA helicase involved in Saccharomyces cerevisiae ribosome assembly. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[36]  K. Browning,et al.  Sequences for two cDNAs encoding Arabidopsis thaliana eukaryotic protein synthesis initiation factor 4A. , 1992, Gene.

[37]  F. Amalric,et al.  Concerted activities of the RNA recognition and the glycine-rich C-terminal domains of nucleolin are required for efficient complex formation with pre-ribosomal RNA. , 1992, European journal of biochemistry.

[38]  N. Sonenberg,et al.  Mutational analysis of a DEAD box RNA helicase: the mammalian translation initiation factor eIF‐4A. , 1992, The EMBO journal.

[39]  N. Perrimon,et al.  Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila. , 1992, Genetics.

[40]  D. Lindsley,et al.  The Genome of Drosophila Melanogaster , 1992 .

[41]  P Linder,et al.  D‐E‐A‐D protein family of putative RNA helicases , 1992, Molecular microbiology.

[42]  N. Perrimon,et al.  Generating lineage-specific markers to study Drosophila development. , 1991, Developmental genetics.

[43]  Y. Jan,et al.  Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila , 1991, Cell.

[44]  T. Orr-Weaver,et al.  The regulation of the cell cycle during Drosophila embryogenesis: the transition to polyteny. , 1991, Development.

[45]  J. Beggs,et al.  A suppressor of yeast spp81/ded1 mutations encodes a very similar putative ATP‐dependent RNA helicase , 1991, Molecular microbiology.

[46]  D. Lane,et al.  p68 RNA helicase: identification of a nucleolar form and cloning of related genes containing a conserved intron in yeasts , 1991, Molecular and cellular biology.

[47]  D. L. Weeks,et al.  The Xenopus localized messenger RNA An3 may encode an ATP-dependent RNA helicase , 1991, Nature.

[48]  J. Abelson,et al.  Requirement of the RNA helicase-like protein PRP22 for release of messenger RNA from spliceosomes , 1991, Nature.

[49]  C. Guthrie,et al.  PRP16 is an RNA-dependent ATPase that interacts transiently with the spliceosome , 1991, Nature.

[50]  J. H. Chen,et al.  The yeast PRP2 protein, a putative RNA-dependent ATPase, shares extensive sequence homology with two other pre-mRNA splicing factors. , 1990, Nucleic acids research.

[51]  J. Abelson,et al.  PRP5: a helicase-like protein required for mRNA splicing in yeast. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[52]  C. Guthrie,et al.  A putative ATP binding protein influences the fidelity of branchpoint recognition in yeast splicing , 1990, Cell.

[53]  R. W. Davis,et al.  Translation initiation and ribosomal biogenesis: involvement of a putative rRNA helicase and RPL46. , 1990, Science.

[54]  A. Pardee.  G1 events and regulation of cell proliferation. , 1989, Science.

[55]  M. Nirenberg,et al.  Drosophila NK-homeobox genes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[56]  M. Scheffner,et al.  RNA helicase activity associated with the human p68 protein , 1989, Nature.

[57]  V. Foe,et al.  Mitotic domains reveal early commitment of cells in Drosophila embryos. , 1989, Development.

[58]  P. Slonimski,et al.  Birth of the D-E-A-D box , 1989, Nature.

[59]  R. Tjian,et al.  Analysis of Sp1 in vivo reveals mutiple transcriptional domains, including a novel glutamine-rich activation motif , 1988, Cell.

[60]  M. Ashburner,et al.  The product of the Drosophila gene vasa is very similar to eukaryotic initiation factor-4A , 1988, Nature.

[61]  F. Kafatos,et al.  Functional cDNA libraries from Drosophila embryos. , 1988, Journal of molecular biology.

[62]  C. Goodman,et al.  Sequence analysis and neuronal expression of fasciclin I in grasshopper and drosophila , 1988, Cell.

[63]  M. Frasch,et al.  Nuclear antigens follow different pathways into daughter nuclei during mitosis in early Drosophila embryos. , 1986, Journal of cell science.

[64]  G K Lewis,et al.  Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product , 1985, Molecular and cellular biology.

[65]  G. Rubin,et al.  Vectors for P element-mediated gene transfer in Drosophila. , 1983, Nucleic acids research.

[66]  G. Morata,et al.  Differential mitotic rates and patterns of growth in compartments in the Drosophila wing. , 1981, Developmental biology.

[67]  G. Morata,et al.  Minutes: mutants of drosophila autonomously affecting cell division rate. , 1975, Developmental biology.

[68]  J. Hershey,et al.  2 The Pathway and Mechanism of Eukaryotic Protein Synthesis , 1996 .

[69]  Z. Xue,et al.  The nucleolus: an organelle formed by the act of building a ribosome. , 1995, Current opinion in cell biology.

[70]  J. Blenis,et al.  The 70 kDa S6 kinase: regulation of a kinase with multiple roles in mitogenic signalling. , 1995, Current opinion in cell biology.

[71]  P. Nurse,et al.  Animal cell cycles and their control. , 1992, Annual review of biochemistry.

[72]  R. Laskey,et al.  Nuclear targeting sequences--a consensus? , 1991, Trends in biochemical sciences.

[73]  R. Eisenman,et al.  Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. , 1991, Science.

[74]  M. Bate,et al.  Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster. , 1988, Developmental biology.

[75]  M. Kay,et al.  Developmental genetics of ribosome synthesis in Drosophila , 1987 .