Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in dyskeratosis congenita

Petar N Grozdanov, Narcis Fernandez-Fuentes, Andras Fiser, U Thomas Meier

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31 Citations (SciVal)


X-linked dyskeratosis congenita (DC) is a rare bone marrow failure syndrome caused by mostly missense mutations in the pseudouridine synthase NAP57 (dyskerin/Cbf5). As part of H/ACA ribonucleoproteins (RNPs), NAP57 is important for the biogenesis of ribosomes, spliceosomal small nuclear RNPs, microRNAs and the telomerase RNP. DC mutations concentrate in the N- and C-termini of NAP57 but not in its central catalytic domain raising questions as to their impact. We demonstrate that the N- and C-termini together form the binding surface for the H/ACA RNP assembly factor SHQ1 and that DC mutations modulate the interaction between the two proteins. Pinpointing impaired interaction between NAP57 and SHQ1 as a potential molecular basis for X-linked DC has implications for therapeutic approaches, e.g. by targeting the NAP57-SHQ1 interface with small molecules.
Original languageEnglish
Pages (from-to)4546-51
Number of pages6
JournalHuman Molecular Genetics
Issue number23
Publication statusPublished - 2009


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