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Molecular and Cellular Biology, November 2004, p. 9646-9657, Vol. 24, No. 21
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.21.9646-9657.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Nuclear Pre-mRNA Decapping and 5' Degradation in Yeast Require the Lsm2-8p Complex

Joanna Kufel,{dagger} Cecile Bousquet-Antonelli,{ddagger} Jean D. Beggs, and David Tollervey*

Wellcome Trust Centre for Cell Biology, The University of Edinburgh, Edinburgh, United Kingdom

Received 25 June 2004/ Returned for modification 14 July 2004/ Accepted 30 July 2004

Previous analyses have identified related cytoplasmic Lsm1-7p and nuclear Lsm2-8p complexes. Here we report that mature heat shock and MET mRNAs that are trapped in the nucleus due to a block in mRNA export were strongly stabilized in strains lacking Lsm6p or the nucleus-specific Lsm8p protein but not by the absence of the cytoplasmic Lsm1p. These nucleus-restricted mRNAs remain polyadenylated until their degradation, indicating that nuclear mRNA degradation does not involve the incremental deadenylation that is a key feature of cytoplasmic turnover. Lsm8p can be UV cross-linked to nuclear poly(A)+ RNA, indicating that an Lsm2-8p complex interacts directly with nucleus-restricted mRNA. Analysis of pre-mRNAs that contain intronic snoRNAs indicates that their 5' degradation is specifically inhibited in strains lacking any of the Lsm2-8p proteins but Lsm1p. Nucleus-restricted mRNAs and pre-mRNA degradation intermediates that accumulate in lsm mutants remain 5' capped. We conclude that the Lsm2-8p complex normally targets nuclear RNA substrates for decapping.

* Corresponding author. Mailing address: Wellcome Trust Centre for Cell Biology, King's Buildings, The 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.

{dagger} Present address: Department of Genetics, Warsaw University, 02-106 Warsaw, Poland.

{ddagger} Present address: GEEM, Université Blaise Pascal, 63177 Aubière, France.

Molecular and Cellular Biology, November 2004, p. 9646-9657, Vol. 24, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.21.9646-9657.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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