Restricting conformational flexibility of the switch II region creates a dominant-inhibitory phenotype in Obg GTPase Nog1

Yevgeniya R. Lapik, Julia M. Misra, Lester F. Lau, Dimitri G. Pestov

    Research output: Contribution to journalArticlepeer-review

    16 Scopus citations

    Abstract

    Nog1 is a conserved eukaryotic GTPase of the Obg family involved in the biogenesis of 60S ribosomal subunits. Here we report the unique dominant-inhibitory properties of a point mutation in the switch II region of mouse Nog1; this mutation is predicted to restrict conformational mobility of the GTP-binding domain. We show that although the mutation does not significantly affect GTP binding, ectopic expression of the mutant in mouse cells disrupts productive assembly of pre-60S subunits and arrests cell proliferation. The mutant impairs processing of multiple pre-rRNA intermediates, resulting in the degradation of the newly synthesized 5.8S/28S rRNA precursors. Sedimentation analysis of nucleolar preribosomes indicates that defective Nog1 function inhibits the conversion of 32S pre-rRNA-containing complexes to a smaller form, resulting in a drastic accumulation of enlarged pre-60S particles in the nucleolus. These results suggest that conformational changes in the switch II element of Nog1 have a critical importance for the dissociation of preribosome-bound factors during intranucleolar maturation and thereby strongly influence the overall efficiency of the assembly process.

    Original languageEnglish (US)
    Pages (from-to)7735-7744
    Number of pages10
    JournalMolecular and Cellular Biology
    Volume27
    Issue number21
    DOIs
    StatePublished - Nov 2007

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Cell Biology

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