Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity.
Retinitis pigmentosa (RP) is a hereditary disease affecting tens of thousands of people world-wide. Here we analyzed the effect of an amino acid substitution in the RNA helicase DHX38 (Prp16) causing RP. DHX38 has been proposed as the helicase important for the 2nd step of splicing. We showed that D...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0265742 |
| _version_ | 1797944015343058944 |
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| author | Mina Obuća Zuzana Cvačková Jan Kubovčiak Michal Kolář David Staněk |
| author_facet | Mina Obuća Zuzana Cvačková Jan Kubovčiak Michal Kolář David Staněk |
| author_sort | Mina Obuća |
| collection | DOAJ |
| description | Retinitis pigmentosa (RP) is a hereditary disease affecting tens of thousands of people world-wide. Here we analyzed the effect of an amino acid substitution in the RNA helicase DHX38 (Prp16) causing RP. DHX38 has been proposed as the helicase important for the 2nd step of splicing. We showed that DHX38 associates with key splicing factors involved in both splicing steps but did not find any evidence that the RP mutations changes DHX38 interaction profile with the spliceosome. We further downregulated DHX38 and monitored changes in splicing. We observed only minor perturbations of general splicing but detected modulation of ~70 alternative splicing events. Next, we probed DHX38 function in splicing of retina specific genes and found that FSCN2 splicing is dependent on DHX38. In addition, RHO splicing was inhibited specifically by expression of DHX38 RP variant. Finally, we showed that overexpression of DHX38 promotes usage of canonical as well as cryptic 5' splice sites in HBB splicing reporter. Together, our data show that DHX38 is a splicing factor that promotes splicing of cryptic splice sites and regulate alternative splicing. We further provide evidence that the RP-linked substitution G332D modulates DHX38 splicing activity. |
| first_indexed | 2024-04-10T20:31:55Z |
| format | Article |
| id | doaj.art-97b72106a67046f88e9acd09c2a7c0d1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-10T20:31:55Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-97b72106a67046f88e9acd09c2a7c0d12023-01-25T05:33:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01174e026574210.1371/journal.pone.0265742Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity.Mina ObućaZuzana CvačkováJan KubovčiakMichal KolářDavid StaněkRetinitis pigmentosa (RP) is a hereditary disease affecting tens of thousands of people world-wide. Here we analyzed the effect of an amino acid substitution in the RNA helicase DHX38 (Prp16) causing RP. DHX38 has been proposed as the helicase important for the 2nd step of splicing. We showed that DHX38 associates with key splicing factors involved in both splicing steps but did not find any evidence that the RP mutations changes DHX38 interaction profile with the spliceosome. We further downregulated DHX38 and monitored changes in splicing. We observed only minor perturbations of general splicing but detected modulation of ~70 alternative splicing events. Next, we probed DHX38 function in splicing of retina specific genes and found that FSCN2 splicing is dependent on DHX38. In addition, RHO splicing was inhibited specifically by expression of DHX38 RP variant. Finally, we showed that overexpression of DHX38 promotes usage of canonical as well as cryptic 5' splice sites in HBB splicing reporter. Together, our data show that DHX38 is a splicing factor that promotes splicing of cryptic splice sites and regulate alternative splicing. We further provide evidence that the RP-linked substitution G332D modulates DHX38 splicing activity.https://doi.org/10.1371/journal.pone.0265742 |
| spellingShingle | Mina Obuća Zuzana Cvačková Jan Kubovčiak Michal Kolář David Staněk Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity. PLoS ONE |
| title | Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity. |
| title_full | Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity. |
| title_fullStr | Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity. |
| title_full_unstemmed | Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity. |
| title_short | Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity. |
| title_sort | retinitis pigmentosa linked mutation in dhx38 modulates its splicing activity |
| url | https://doi.org/10.1371/journal.pone.0265742 |
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