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Mourao, A. ; Varrot, A.* ; Mackereth, C.D.* ; Cusack, S.* ; Sattler, M.

Structure and RNA recognition by the snRNA and snoRNA transport factor PHAX.

RNA 16, 1205-1216 (2010)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Small nuclear and small nucleolar RNAs (snRNAs and snoRNAs) are critical components of snRNPs and snoRNPs and play an essential role in the maturation of, respectively, mRNAs and rRNAs within the nucleus of eukaryotic cells. Complex and specific pathways exist for the assembly of snRNPs and snoRNPs, involving, for instance, nucleocytoplasmic transport of snRNAs and intranuclear transport between compartments of snoRNAs. The phosphorylated adaptor for nuclear export (PHAX) is required for nuclear export of snRNAs in metazoans and also involved in the intranuclear transport of snoRNAs to Cajal bodies. PHAX contains a conserved single-stranded nucleic acid binding domain (RNA_GG_bind domain) with no sequence homology with any other known RNA-binding module. Here, we report NMR and X-ray crystallography studies that elucidate the structural basis for RNA recognition by the PHAX RNA-binding domain (PHAX-RBD). The crystal structure of the RNA_GG_bind domain from the parasite Cryptosporidium parvum (Cp RBD) forms well-folded dimers in solution in the absence of any ligand. The human PHAX-RBD is monomeric and only adopts a tertiary fold upon RNA binding. The PHAX-RBD represents a novel helical fold and binds single-stranded RNA with micromolar affinity without sequence specificity. RNA recognition by human PHAX-RBD is consistent with mutational analysis that affects RNA binding and PHAX-mediated nuclear export. Our data suggest that the PHAX-RBD mediates auxiliary RNA contacts with the snRNA and snoRNA substrates that are required for transport and/or substrate release.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Nuclear export; PHAX; Protein-RNA; snRNA; Structural biology
ISSN (print) / ISBN 1355-8382
e-ISSN 1469-9001
Zeitschrift RNA
Quellenangaben Band: 16, Heft: 6, Seiten: 1205-1216 Artikelnummer: , Supplement: ,
Verlag Cold Spring Harbor Laboratory Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)