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Molecular and Cellular Biology, September 2008, p. 5446-5457, Vol. 28, No. 17
0270-7306/08/$08.00+0     doi:10.1128/MCB.00463-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Yeast Exosome Cofactor, Mpp6, Functions in RNA Surveillance and in the Degradation of Noncoding RNA Transcripts{triangledown}

Laura Milligan,3 Laurence Decourty,1 Cosmin Saveanu,1 Juri Rappsilber,3 Hugo Ceulemans,2 Alain Jacquier,1 and David Tollervey3*

Institut Pasteur, Unité de Génétique des Interactions Macromoléculaires, URA 2171-CNRS, 28 Rue du Dr. Roux, F-75724 Paris cedex 15, France,1 Department for Molecular Cell Biology, Katholieke Universiteit Leuven, Campus Gasthuisberg O&N1-901, Herestraat 49, B-3000 Leuven, Belgium,2 Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom3

Received 20 March 2008/ Returned for modification 14 April 2008/ Accepted 18 June 2008

A genome-wide screen for synthetic lethal (SL) interactions with loss of the nuclear exosome cofactors Rrp47/Lrp1 or Air1 identified 3'->5' exonucleases, the THO complex required for mRNP assembly, and Ynr024w (Mpp6). SL interactions with mpp6{Delta} were confirmed for rrp47{Delta} and nuclear exosome component Rrp6. The results of bioinformatic analyses revealed homology between Mpp6 and a human exosome cofactor, underlining the high conservation of the RNA surveillance system. Mpp6 is an RNA binding protein that physically associates with the exosome and was localized throughout the nucleus. The results of functional analyses demonstrated roles for Mpp6 in the surveillance of both pre-rRNA and pre-mRNAs and in the degradation of "cryptic" noncoding RNAs (ncRNAs) derived from intergenic regions and the ribosomal DNA spacer heterochromatin. Strikingly, these ncRNAs are also targeted by other exosome cofactors, including Rrp47, the TRAMP complex (which includes Air1), and the Nrd1/Nab3 complex, and are degraded by both Rrp6 and the core exosome. Heterochromatic transcripts and other ncRNAs are characterized by very rapid degradation, and we predict that functional redundancy is an important feature of ncRNA metabolism.

* 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

{triangledown} Published ahead of print on 30 June 2008.

Molecular and Cellular Biology, September 2008, p. 5446-5457, Vol. 28, No. 17
0270-7306/08/$08.00+0     doi:10.1128/MCB.00463-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lykke-Andersen, S., Brodersen, D. E., Jensen, T. H. (2009). Origins and activities of the eukaryotic exosome. J. Cell Sci. 122: 1487-1494 [Abstract] [Full Text]  
  • Venters, B. J., Pugh, B. F. (2009). A canonical promoter organization of the transcription machinery and its regulators in the Saccharomyces genome. Genome Res 19: 360-371 [Abstract] [Full Text]  


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