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Molecular and Cellular Biology, March 2005, p. 1577-1585, Vol. 25, No. 5
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.5.1577-1585.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Nuclear Exosome Contributes to Autogenous Control of NAB2 mRNA Levels

Departments of Microbiology and Immunology and Biochemistry and Biophysics,¹ University of Rochester School of Medicine and Dentistry, Rochester, New York²

Received 22 October 2004/ Returned for modification 15 November 2004/ Accepted 1 December 2004

The RNA-processing exosome is a complex of riboexonucleases required for 3'-end formation of some noncoding RNAs and for the degradation of mRNAs in eukaryotes. The nuclear form of the exosome functions in an mRNA surveillance pathway that retains and degrades improperly processed precursor mRNAs within the nucleus. We report here that the nuclear exosome controls the level of NAB2 mRNA, encoding the nuclear poly(A)⁺-RNA-binding protein Nab2p. Mutations affecting the activity of the nuclear, but not the cytoplasmic, exosome cause an increase in the amount of NAB2 mRNA. Cis- and trans-acting mutations that inhibit degradation by the nuclear-exosome subunit Rrp6p result in elevated levels of NAB2 mRNA. Control of NAB2 mRNA levels occurs posttranscriptionally and requires a sequence of 26 consecutive adenosines (A₂₆) in the NAB2 3' untranslated region, which represses NAB2 3'-end formation and sensitizes the transcript to degradation by Rrp6p. Analysis of NAB2 mRNA levels in a nab2-1 mutant and in the presence of excess Nab2p indicates that Nab2p activity negatively controls NAB2 mRNA levels in an A₂₆- and Rrp6p-dependent manner. These findings suggest a novel regulatory circuit in which the nuclear exosome controls the level of NAB2 mRNA in response to changes in the activity of Nab2 protein.

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