Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00558860" target="_blank" >RIV/68378050:_____/22:00558860 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11310/22:10457697
Result on the web
<a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0265742" target="_blank" >https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0265742</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1371/journal.pone.0265742" target="_blank" >10.1371/journal.pone.0265742</a>

Result language
angličtina
Original language name
Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity
Original language 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 2(nd) 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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10601 - Cell biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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