title: Poly(ADP-ribose) glycohydrolase and poly(ADP-ribose)-interacting protein Hrp38 regulate pattern formation during Drosophila eye development.
abstract: Drosophila Hrp38, a homolog of human hnRNP A1, has been shown to regulate splicing, but its function can be modified by poly(ADP-ribosyl)ation. Notwithstanding such findings, our understanding of the roles of poly(ADP-ribosyl)ated Hrp38 on development is limited. Here, we have demonstrated that Hrp38 is essential for fly eye development based on a rough-eye phenotype with disorganized ommatidia observed in adult escapers of the hrp38 mutant. We also observed that poly(ADP-ribose) glycohydrolase (Parg) loss-of-function, which caused increased Hrp38 poly(ADP-ribosyl)ation, also resulted in the rough-eye phenotype with disrupted ommatidial lattice and reduced number of photoreceptor cells. In addition, ectopic expression of DE-cadherin, which is required for retinal morphogenesis, fully rescued the rough-eye phenotype of the hrp38 mutant. Similarly, Parg mutant eye clones had decreased expression level of DE-cadherin with orientation defects, which is reminiscent of DE-cadherin mutant eye phenotype. Therefore, our results suggest that Hrp38 poly(ADP-ribosyl)ation controls eye pattern formation via regulation of DE-cadherin expression, a finding which has implications for understanding the pathogenic mechanisms of Hrp38-related Fragile X syndrome and PARP1-related retinal degeneration diseases.
authors.affiliation: Cancer Biology Program, Epigenetics and Progenitor Cell Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Yingbiao
authors.initials: Y
authors.lastname: Ji
authors.forename: Michael
authors.initials: M
authors.lastname: Jarnik
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Tulin
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005123:Eye / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D015870:Gene Expression; D006026:Glycoside Hydrolases / Q000378:metabolism*; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009154:Mutation; D010641:Phenotype; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C097984:HRB98DE protein, Drosophila; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012261:Ribonucleoproteins; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase
keywords: 5′ untranslated region; 5′UTR; DE-cadherin; Df; Drosophila; Drosophila epithelial cadherin; ESEs; ESSs; Eye development; GSC; Hrp38; ISEs; ISSs; PARG; PARP1; Pattern formation; RP; SR protein; UAS; deficiency; exonic splicing enhancers; exonic splicing silencers; germline stem cell; heterogeneous nuclear ribonucleoproteins; hnRNP/Hrp; intronic splicing enhancers; intronic splicing silencers; pADPr; poly(ADP-ribose); poly(ADP-ribose) glycohydrolase; poly(ADP-ribose) polymerase 1; poly(ADP-ribosyl)ation; rd1; retinal degeneration 1; retinitis pigmentosa; serine-arginine-rich protein; upstream activation sequence