A mutation linked to retinitis pigmentosa in HPRP31 causes protein instability and impairs its interactions with spliceosomal snRNPs

0334100 - ÚMG 2010 RIV GB eng J - Článek v odborném periodiku
Huranová, Martina - Hnilicová, Jarmila - Fleischer, Branislav - Cvačková, Zuzana - Staněk, David
A mutation linked to retinitis pigmentosa in HPRP31 causes protein instability and impairs its interactions with spliceosomal snRNPs.
Human Molecular Genetics. Roč. 18, č. 11 (2009), s. 2014-2023. ISSN 0964-6906. E-ISSN 1460-2083
Grant CEP: GA AV ČR KAN200520801
Grant ostatní: Max Planck Society(DE) Partner group program
Výzkumný záměr: CEZ:AV0Z50520514
Klíčová slova: retinitis pigmentosa * snRNP * splicing
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 7.386, rok: 2009

The AD29 mutation in HPRP31 belongs to a series of mutations that were initially linked with the autosomal dominant disorder retinitis pigmentosa (RP) type 11. The HPRP31 gene encodes the hPrp31 protein that specifically associates with spliceosomal small nuclear ribonucleoprotein particles (snRNPs). In this study we report that expression of this mutant protein affects cell proliferation and alters the structure of nuclear Cajal bodies that are connected with snRNP metabolism. Interestingly, these effects can be reversed by the over-expression of the hPrp6 protein, a binding partner of hPrp31. We present several lines of evidence that demonstrate that association between the AD29 mutant and snRNPs in the cell nucleus is significantly reduced. Finally, we show that stability of the AD29 mutant is severely affected resulting in its rapid degradation. Taken together, our results significantly impact our understanding of the molecular mechanisms underlying RP.
Trvalý link: http://hdl.handle.net/11104/0178923