Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in dyskeratosis congenita

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

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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 (US)
Pages (from-to)4546-4551
Number of pages6
JournalHuman molecular genetics
Volume18
Issue number23
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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