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Molecular and Cellular Biology, November 2007, p. 7735-7744, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.01161-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Restricting Conformational Flexibility of the Switch II Region Creates a Dominant-Inhibitory Phenotype in Obg GTPase Nog1{triangledown}

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

Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago College of Medicine, Chicago, Illinois 60607

Received 28 June 2007/ Returned for modification 27 July 2007/ Accepted 27 August 2007

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.

* Corresponding author. Present address: Department of Cell Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, 2 Medical Center Drive, Stratford, NJ 08084. Phone: (856) 566-6904. Fax: (856) 566-2881. E-mail: pestovdg{at}umdnj.edu

{triangledown} Published ahead of print on 4 September 2007.

Molecular and Cellular Biology, November 2007, p. 7735-7744, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.01161-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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