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Molecular and Cellular Biology, November 2005, p. 9859-9873, Vol. 25, No. 22
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.22.9859-9873.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Novel ATP-Binding Cassette Protein ARB1 Is a Shuttling Factor That Stimulates 40S and 60S Ribosome Biogenesis

Jinsheng Dong,¹ Ruby Lai,¹ Jennifer L. Jennings,² Andrew J. Link,² and Alan G. Hinnebusch^1*

Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, Bethesda, Maryland 20892,¹ Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8575²

Received 9 June 2005/ Returned for modification 5 July 2005/ Accepted 15 August 2005

ARB1 is an essential yeast protein closely related to members of a subclass of the ATP-binding cassette (ABC) superfamily of proteins that are known to interact with ribosomes and function in protein synthesis or ribosome biogenesis. We show that depletion of ARB1 from Saccharomyces cerevisiae cells leads to a deficit in 18S rRNA and 40S subunits that can be attributed to slower cleavage at the A0, A1, and A2 processing sites in 35S pre-rRNA, delayed processing of 20S rRNA to mature 18S rRNA, and a possible defect in nuclear export of pre-40S subunits. Depletion of ARB1 also delays rRNA processing events in the 60S biogenesis pathway. We further demonstrate that ARB1 shuttles from nucleus to cytoplasm, cosediments with 40S, 60S, and 80S/90S ribosomal species, and is physically associated in vivo with TIF6, LSG1, and other proteins implicated previously in different aspects of 60S or 40S biogenesis. Mutations of conserved ARB1 residues expected to function in ATP hydrolysis were lethal. We propose that ARB1 functions as a mechanochemical ATPase to stimulate multiple steps in the 40S and 60S ribosomal biogenesis pathways.

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* Corresponding author. Mailing address: National Institutes of Health, Building 6A/Room B1A13, Bethesda, MD 20892. Phone: (301) 496-4480. Fax: (301) 496-6828. E-mail: ahinnebusch{at}nih.gov.

Supplemental material for this article may be found at http://mcb.asm.org/.

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Molecular and Cellular Biology, November 2005, p. 9859-9873, Vol. 25, No. 22
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.22.9859-9873.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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