Assessment of gene expression levels upon overexpession of Retinitis pigmentosa associated Prp8 mutant proteins in the Drosophila eye antennal imaginal discs
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PROVIDER: PRJNA579375 | ENA |
REPOSITORIES: ENA
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Project description:Retinitis pigmentosa (RP) represents a heterogeneous group of hereditary eye disorders characterized by a progressive loss of vision. Mutations in thirty different genes have been linked to the autosomal dominant form of RP (adRP), with nearly one-quarter of them encoding the core components of the spliceosome, a macromolecular machine that removes introns from nascent pre-mRNAs, generating mature transcripts. Here we establish the Drosophila melanogaster model for RP13 linked to the mutations in the most conserved protein of the spliceosome, PRPF8/Prp8. We demonstrate negative impact of the nine different RP-associated Prp8 mutant proteins on the developmental timing when expressed in the endocrine cells specialized to produce the major insect molting hormone. In the developing eye primordium, actively cycling cells rather than differentiated photoreceptors showed sensitivity to Prp8 malfunction. The overexpression of the two most toxic RP variants Prp8S>F and Prp8H>R induced apoptosis and disturbances of the adult eye morphology. While the affected tissue mounted the stress and cytoprotective response, the genetic programs underlying neuronal function were attenuated. Importantly, the expressivity and penetrance among the RP-Prp8 mutations differed and increased under prp8 heterozygosity.
2020-06-16 | GSE139361 | GEO
Project description:Transcriptomes of Drosophila melanogaster eye-antennal imaginal discs at three sequential larval stages: late 2nd instar (72h after egg laying (AEL)), mid 3rd instar (96h AEL) and late 3rd instar (120h AEL).
2018-01-08 | GSE94915 | GEO
Project description:In this study we use Tag-sequencing in eye-antennal and wing imaginal discs across Drosophila species to determine a set of conserved eye-specific developmental genes. Next, we perform motif discovery analysis using the tool i-cisTarget, to depict the core gene developmental network underlying compound eye photoreceptor. The Glass position weight matrix appears as the most highly overrepresented motif, thus positioning Glass as a master regulator in compound eye photoreceptor development. Differential gene expression analysis by RNA-seq in D.melanogaster wild-type eye-antennal versus glass mutant [gl 60j] shows that the majority of our predicted Glass targets show strong downregulation in the glass mutant. This SuperSeries is composed of the following subset Series: GSE39781: RNA-seq in wild-type and glass mutant eye-antennal discs in Drosophila melanogaster GSE39782: Tag-seq profiling in eye-antennal and wing imaginal discs of D. melanogaster, D. yakuba and D. virilis
2012-09-21 | E-GEOD-39784 | biostudies-arrayexpress
Project description:In this study we use Tag-sequencing in eye-antennal and wing imaginal discs across Drosophila species to determine a set of conserved eye-specific developmental genes. Next, we perform motif discovery analysis using the tool i-cisTarget, to depict the core gene developmental network underlying compound eye photoreceptor. The Glass position weight matrix appears as the most highly overrepresented motif, thus positioning Glass as a master regulator in compound eye photoreceptor development. Differential gene expression analysis by RNA-seq in D.melanogaster wild-type eye-antennal versus glass mutant [gl 60j] shows that the majority of our predicted Glass targets show strong downregulation in the glass mutant. This SuperSeries is composed of the SubSeries listed below.
2012-09-21 | GSE39784 | GEO
Project description:The goal of this study is to identify co-expressed genes downstream of Atonal and Senseless. These gene lists are used as candidate target genes (technically: as foreground sets) in computational predictions of cis-regulatory elements using the cisTargetX method (http://med.kuleuven.be/cme-mg/lng/cisTargetX). Together, the gene expression results and cis-regulatory predictions, yield a gene regulatory network underlying the early events in retinal differentiation. Predicted cis-regulatory interactions have been validated extensively in vivo using enhancer reporter assays and genetic perturbations. Six samples were analyzed for Atonal gain-of-function (GOF) in the eye-antennal imaginal discs of third instar larvae of Drosophila melanogaster, namely three biological repeats for two different Gal4 drivers (Gal4/7 and AtoGal), crossed with UASato. Three samples were analyzed for Atonal loss-of-function (LOF) in the eye-antennal imaginal discs, namely three biological repeats of ato-/- larvae. Three samples were analyzed for Senseless GOF, namely three biological repeats of atoGal4 crossed with UASsens. Finally, eight control samples were analyzed, namely two biological repeats of four different lines (atoGal4, Gal4/7, UASato, and cantonS wild type).
2010-07-29 | E-GEOD-16713 | biostudies-arrayexpress
Project description:Recessive retinitis pigmentosa (RP) is often caused by nonsense mutations that lead to low mRNA levels as a result of nonsense-mediated decay. Some RP genes are expressed at detectable levels in leukocytes as well as in the retina. We designed a microarray-based method to find recessive RP genes based on low lymphoblast mRNA expression levels Keywords: Recessive mutations; mRNA expression; nonsense mediated-decay; retinitis pigmentosa; lymphocyte; Affymetrix genechip Human Genome U133Plus2.0.
2008-07-14 | GSE12086 | GEO
Project description:A Drosophila mutant for the splicing factor Prp31 was generated and characterized as a model for Retinitis pigmentosa 11. The transcriptome of the mutant was compared to the genetic control white.
2019-01-01 | GSE99665 | GEO
Project description:The essential process of pre-mRNA splicing must occur with high fidelity and efficiency for proper gene expression. The spliceosome employs DExD/H box helicases to promote on-pathway interactions while simultaneously minimizing errors. Prp8 and Snu114, an EF2-like GTPase, regulate the activity of the Brr2 helicase, promoting RNA unwinding by Brr2 at appro-priate points in the splicing cycle and repressing it at others. Mutations linked to Retinitis Pig-mentosa (RP), a disease that causes blindness in humans, map to the Brr2 regulatory region of Prp8. Previous In vitro studies of homologous mutations in Saccharomyces cerevisiae show that Prp8-RP mutants cause defects in spliceosome activation. Here we show a subset of RP muta-tions in Prp8 also cause defects in the transition between the 1st and 2nd catalytic steps of splic-ing. Though Prp8-RP mutants do not cause defects in splicing fidelity, they result in an overall decrease in splicing efficiency. Furthermore, genetic analyses link Snu114 GTP/GDP occupancy to Prp8-dependent regulation of Brr2. Our results implicate the transition between the 1st and 2nd catalytic steps as a critical place in the splicing cycle where Prp8-RP mutants influence splic-ing efficiency. The location of the Prp8-RP mutants, at the “hinge” that links the Prp8 Jab1-MPN regulatory “tail” to the globular portion of the domain, suggests that these Prp8-RP mutants inhibit regulated movement of the Prp8 Jab1/MPN domain into the Brr2 RNA binding channel to transiently inhibit Brr2 activity. Therefore, in Prp8-linked RP, disease likely results not only from defects in spliceosome assembly and activation, but also because of defects in splicing ca-talysis. paper to be submitted
2016-07-21 | GSE75081 | GEO
Project description:The essential process of pre-mRNA splicing must occur with high fidelity and efficiency for proper gene expression. The spliceosome employs DExD/H box helicases to promote on-pathway interactions while simultaneously minimizing errors. Prp8 and Snu114, an EF2-like GTPase, regulate the activity of the Brr2 helicase, promoting RNA unwinding by Brr2 at appro-priate points in the splicing cycle and repressing it at others. Mutations linked to Retinitis Pig-mentosa (RP), a disease that causes blindness in humans, map to the Brr2 regulatory region of Prp8. Previous In vitro studies of homologous mutations in Saccharomyces cerevisiae show that Prp8-RP mutants cause defects in spliceosome activation. Here we show a subset of RP muta-tions in Prp8 also cause defects in the transition between the 1st and 2nd catalytic steps of splic-ing. Though Prp8-RP mutants do not cause defects in splicing fidelity, they result in an overall decrease in splicing efficiency. Furthermore, genetic analyses link Snu114 GTP/GDP occupancy to Prp8-dependent regulation of Brr2. Our results implicate the transition between the 1st and 2nd catalytic steps as a critical place in the splicing cycle where Prp8-RP mutants influence splic-ing efficiency. The location of the Prp8-RP mutants, at the â??hingeâ?? that links the Prp8 Jab1-MPN regulatory â??tailâ?? to the globular portion of the domain, suggests that these Prp8-RP mutants inhibit regulated movement of the Prp8 Jab1/MPN domain into the Brr2 RNA binding channel to transiently inhibit Brr2 activity. Therefore, in Prp8-linked RP, disease likely results not only from defects in spliceosome assembly and activation, but also because of defects in splicing ca-talysis. paper to be submitted Two channel microarrays were used. RNA isolated from wt yeast grown simultaneously to the mutant was used as a reference. This reference was used in one of the channels for each hybridization and used in the statistical analysis to obtain an average expression-profile for each mutant relative to the wt. Three independent cultures were hybridized on two separate microarrays. For the first hybridization the Cy5 (red) labeled cRNA from the mutant is hybridized together with the Cy3 (green) labeled cRNA from the common reference. For the replicate hybridization, the labels are swapped. Each gene is represented twice on the microarray, resulting in four measurements per mutant. Strains, both WT and mutant, were grown at 37C until mid-log phase, OD600 of approximately 0.7. The mutated PRP8 gene is present on HIS marked CEN plasmid, and the corresponding genomic copy of PRP8 deleted. Strains labeled as wildtype also have the relevant genomic PRP8 deleted, but complemented with wildtype PRP8 on CEN plasmid.
2016-07-21 | E-GEOD-75081 | biostudies-arrayexpress
Project description:Experiment to examine the miRNA profiles in the retina compared to the brain and other body regions. A comparison of a wild type C57 mouse retina versus a retina from a mouse model of retinitis pigmentosa (Pro347Ser) was under taken.
2007-11-22 | E-TABM-332 | biostudies-arrayexpress