Mutations in the splicing regulator Prp31 lead to retinal degeneration in Drosophila
Retinitis pigmentosa (RP) is a clinically heterogeneous disease affecting 1.6 million people worldwide. The second-largest group of genes causing autosomal dominant RP in human encodes regulators of the splicing machinery. Yet, how defects in splicing factor genes are linked to the aetiology of the...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2021-01-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/10/1/bio052332 |
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| author | Sarita Hebbar Malte Lehmann Sarah Behrens Catrin Hälsig Weihua Leng Michaela Yuan Sylke Winkler Elisabeth Knust |
| author_facet | Sarita Hebbar Malte Lehmann Sarah Behrens Catrin Hälsig Weihua Leng Michaela Yuan Sylke Winkler Elisabeth Knust |
| author_sort | Sarita Hebbar |
| collection | DOAJ |
| description | Retinitis pigmentosa (RP) is a clinically heterogeneous disease affecting 1.6 million people worldwide. The second-largest group of genes causing autosomal dominant RP in human encodes regulators of the splicing machinery. Yet, how defects in splicing factor genes are linked to the aetiology of the disease remains largely elusive. To explore possible mechanisms underlying retinal degeneration caused by mutations in regulators of the splicing machinery, we induced mutations in Drosophila Prp31, the orthologue of human PRPF31, mutations in which are associated with RP11. Flies heterozygous mutant for Prp31 are viable and develop normal eyes and retina. However, photoreceptors degenerate under light stress, thus resembling the human disease phenotype. Degeneration is associated with increased accumulation of the visual pigment rhodopsin 1 and increased mRNA levels of twinfilin, a gene associated with rhodopsin trafficking. Reducing rhodopsin levels by raising animals in a carotenoid-free medium not only attenuates rhodopsin accumulation, but also retinal degeneration. Given a similar importance of proper rhodopsin trafficking for photoreceptor homeostasis in human, results obtained in flies presented here will also contribute to further unravel molecular mechanisms underlying the human disease. This paper has an associated First Person interview with the co-first authors of the article. |
| first_indexed | 2024-12-17T05:05:05Z |
| format | Article |
| id | doaj.art-6d6ef59b3e864ad98c68efb472a629af |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-17T05:05:05Z |
| publishDate | 2021-01-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-6d6ef59b3e864ad98c68efb472a629af2022-12-21T22:02:27ZengThe Company of BiologistsBiology Open2046-63902021-01-0110110.1242/bio.052332052332Mutations in the splicing regulator Prp31 lead to retinal degeneration in DrosophilaSarita Hebbar0Malte Lehmann1Sarah Behrens2Catrin Hälsig3Weihua Leng4Michaela Yuan5Sylke Winkler6Elisabeth Knust7 Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany Retinitis pigmentosa (RP) is a clinically heterogeneous disease affecting 1.6 million people worldwide. The second-largest group of genes causing autosomal dominant RP in human encodes regulators of the splicing machinery. Yet, how defects in splicing factor genes are linked to the aetiology of the disease remains largely elusive. To explore possible mechanisms underlying retinal degeneration caused by mutations in regulators of the splicing machinery, we induced mutations in Drosophila Prp31, the orthologue of human PRPF31, mutations in which are associated with RP11. Flies heterozygous mutant for Prp31 are viable and develop normal eyes and retina. However, photoreceptors degenerate under light stress, thus resembling the human disease phenotype. Degeneration is associated with increased accumulation of the visual pigment rhodopsin 1 and increased mRNA levels of twinfilin, a gene associated with rhodopsin trafficking. Reducing rhodopsin levels by raising animals in a carotenoid-free medium not only attenuates rhodopsin accumulation, but also retinal degeneration. Given a similar importance of proper rhodopsin trafficking for photoreceptor homeostasis in human, results obtained in flies presented here will also contribute to further unravel molecular mechanisms underlying the human disease. This paper has an associated First Person interview with the co-first authors of the article.http://bio.biologists.org/content/10/1/bio052332spliceosomephotoreceptor cellsrhodopsinscarlettwinfilin |
| spellingShingle | Sarita Hebbar Malte Lehmann Sarah Behrens Catrin Hälsig Weihua Leng Michaela Yuan Sylke Winkler Elisabeth Knust Mutations in the splicing regulator Prp31 lead to retinal degeneration in Drosophila Biology Open spliceosome photoreceptor cells rhodopsin scarlet twinfilin |
| title | Mutations in the splicing regulator Prp31 lead to retinal degeneration in Drosophila |
| title_full | Mutations in the splicing regulator Prp31 lead to retinal degeneration in Drosophila |
| title_fullStr | Mutations in the splicing regulator Prp31 lead to retinal degeneration in Drosophila |
| title_full_unstemmed | Mutations in the splicing regulator Prp31 lead to retinal degeneration in Drosophila |
| title_short | Mutations in the splicing regulator Prp31 lead to retinal degeneration in Drosophila |
| title_sort | mutations in the splicing regulator prp31 lead to retinal degeneration in drosophila |
| topic | spliceosome photoreceptor cells rhodopsin scarlet twinfilin |
| url | http://bio.biologists.org/content/10/1/bio052332 |
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