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Molecular and Cellular Biology, November 2005, p. 9996-10004, Vol. 25, No. 22
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.22.9996-10004.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Nuclear Surveillance Pathway for mRNAs with Defective Polyadenylation

Laura Milligan,{dagger} Claire Torchet,{dagger},{ddagger} Christine Allmang,§ Tracey Shipman, and David Tollervey*

Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom

Received 11 March 2005/ Returned for modification 27 April 2005/ Accepted 10 August 2005

The pap1-5 mutation in poly(A) polymerase causes rapid depletion of mRNAs at restrictive temperatures. Residual mRNAs are polyadenylated, indicating that Pap1-5p retains at least partial activity. In pap1-5 strains lacking Rrp6p, a nucleus-specific component of the exosome complex of 3'-5' exonucleases, accumulation of poly(A)+ mRNA was largely restored and growth was improved. The catalytically inactive mutant Rrp6-1p did not increase growth of the pap1-5 strain and conferred much less mRNA stabilization than rrp6{Delta}. This may indicate that the major function of Rrp6p is in RNA surveillance. Inactivation of core exosome components, Rrp41p and Mtr3p, or the nuclear RNA helicase Mtr4p gave different phenotypes, with accumulation of deadenylated and 3'-truncated mRNAs. We speculate that slowed mRNA polyadenylation in the pap1-5 strain is detected by a surveillance activity of Rrp6p, triggering rapid deadenylation and exosome-mediated degradation. In wild-type strains, assembly of the cleavage and polyadenylation complex might be suboptimal at cryptic polyadenylation sites, causing slowed polyadenylation.


* Corresponding author. Mailing address: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom. Phone: (44) 131 650 7092. Fax: (44) 131 650 7040. E-mail: d.tollervey{at}ed.ac.uk.

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

{dagger} These authors contributed equally to the work.

{ddagger} Present address: Unité de Génétique des Interactions Macromoléculaires, URA 2171-CNRS, Institut Pasteur, 25-28 rue du Docteur ROUX, F-75724 Paris Cedex 15, France.

§ Present address: UPR 9002 du CNRS, Institut de Biologie Moleculaire et Cellulaire, 15 rue Rene Descartes, F-67084 Strasbourg Cedex, France.


Molecular and Cellular Biology, November 2005, p. 9996-10004, Vol. 25, No. 22
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.22.9996-10004.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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