title: A role for the serine/arginine-rich (SR) protein B52/SRSF6 in cell growth and myc expression in Drosophila.
abstract: Serine-/arginine-rich (SR) proteins are RNA-binding proteins that are primarily involved in alternative splicing. Expression of some SR proteins is frequently upregulated in tumors, and previous reports have demonstrated that these proteins can directly participate in cell transformation. Identifying factors that can rescue the effects of SR overexpression in vivo is, therefore, of potential therapeutic interest. Here, we analyzed phenotypes induced by overexpression of the SR protein B52 during Drosophila development and identified several proteins that can rescue these phenotypes. Using the mechanosensory bristle lineage as a developmental model, we show that B52 expression level influences cell growth, but not differentiation, in this lineage. In particular, B52 overexpression increases cell growth, upregulates myc transcription, and gives rise to flies lacking thoracic bristles. Using a genetic screen, we identified several suppressors of the phenotypes induced by overexpression of B52 in vivo in two different organs. We show that upregulation of brain tumor (brat), a tumor suppressor and post-transcriptional repressor of myc, and downregulation of lilliputian (lilli), a subunit of the superelongation complex involved in transcription elongation, efficiently rescue the phenotypes induced by B52 overexpression. Our results demonstrate a role of this SR protein in cell growth and identify candidate proteins that may overcome the effects of SR protein overexpression in mammals.
authors: Institut de Génétique Moléculaire de Montpellier, Unité Mixte de Recherche 5535, Centre National de la Recherche Scientifique, 1919 route de Mende, 34293 Montpellier Cedex 5, France Université de Montpellier, 163 rue Auguste Broussonnet, 34090 Montpellier, France.
authors: Céline
authors: C
authors: Fernando
authors: Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7622, Laboratoire de Biologie du Développement, F-75005, Paris, France.
authors: Agnès
authors: A
authors: Audibert
authors: Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7622, Laboratoire de Biologie du Développement, F-75005, Paris, France.
authors: Françoise
authors: F
authors: Simon
authors: Institut de Génétique Moléculaire de Montpellier, Unité Mixte de Recherche 5535, Centre National de la Recherche Scientifique, 1919 route de Mende, 34293 Montpellier Cedex 5, France Université de Montpellier, 163 rue Auguste Broussonnet, 34090 Montpellier, France francois.juge@igmm.cnrs.fr jamal.tazi@igmm.cnrs.fr.
authors: Jamal
authors: J
authors: Tazi
authors: Institut de Génétique Moléculaire de Montpellier, Unité Mixte de Recherche 5535, Centre National de la Recherche Scientifique, 1919 route de Mende, 34293 Montpellier Cedex 5, France Université de Montpellier, 163 rue Auguste Broussonnet, 34090 Montpellier, France francois.juge@igmm.cnrs.fr jamal.tazi@igmm.cnrs.fr.
authors: François
authors: F
authors: Juge
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D048708:Cell Growth Processes; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008465:Mechanoreceptors / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D000072260:RNA Splicing Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D000072260:RNA Splicing Factors; D014157:Transcription Factors; C412783:brat protein, Drosophila; C423386:lilli protein, Drosophila; C070791:B52 protein, Drosophila
keywords: Myc; SR protein; cell growth; genetic screen