Journal Article

Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in dyskeratosis congenita

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

in Human Molecular Genetics

Volume 18, issue 23, pages 4546-4551
Published in print December 2009 | ISSN: 0964-6906
Published online September 2009 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddp416
Pathogenic NAP57 mutations decrease ribonucleoprotein assembly in dyskeratosis congenita

Show Summary Details

Preview

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.

Journal Article.  3542 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.