Počet záznamů: 1

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

  1. 1.
    0334100 - UMG-J 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
    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