Possible Involvement of Proteasomes (Prosomes) in AUUUA-mediated mRNA Decay*
- Anne-Sophie Jarrousse‡,
- Franck Petit‡,
- Claudia Kreutzer-Schmid‡,
- Roger Gaedigk§ and
- Hans-Peter Schmid‡¶
- From the ‡Equipe “Protéasome et Auto-Surveillance Cellulaire” OVGV UA INRA 987, UniversitéBlaise Pascal, Clermont-Ferrand II, 24 avenue des Landais 63177, Aubière cedex, France and the §Biologisches Institut, University of Stuttgart, Pfaffenwaldring 47, D-70569 Stuttgart 80, Germany
Abstract
We have identified a cellular target for proteasomal endonuclease activity. Thus, 20 S proteasomes interact with the 3′-untranslated region of certain cytoplasmic mRNAs in vivo, and 20 S proteasomes isolated from Friend leukemia virus-infected mouse spleen cells were found to be associated with a mRNA fragment showing great homology to the 3′-untranslated region of tumor necrosis factor-β mRNA that contains AUUUA sequences. We furthermore demonstrate that 20 S proteasomes destabilize oligoribonucleotides corresponding to the 3′-untranslated region of tumor necrosis factor-α, creating a specific cleavage pattern. The cleavage reaction is accelerated with increasing number of AUUUA motifs, and major cleavage sites are localized at the 5′ side of the A residues. These results strongly suggest that 20 S proteasomes could be involved in the destabilization of cytokine mRNAs such as tumor necrosis factor mRNAs and other short-lived mRNAs containing AUUUA sequences.
Footnotes
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↵* This work was supported in part by the European Community Biomed II Programm, the Hasselblad Foundation, the Ministère de la Recherche et de la Technologie, the Conseil Régional d’Auvergne, and the Fondation pour la Recherche Médicale (Sidaction), France.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF109292.
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↵¶ To whom correspondence should be addressed. Tel.: 33-4-73-40-51-03; Fax: 33-4-73-40-51-03; E-mail address:hpschmid{at}cicsun.univbpclermont.fr.
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↵2 F. Petit, A.-S. Jarrousse, C. Kreutzer-Schmid, R. Gaedigk, and H.-P. Schmid, unpublished results.
- Abbreviations:
- UTR
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untranslated region
- ARE
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adenosine- and uridine-rich element
- FPLC
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fast protein liquid chromatography
- TNF
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tumor necrosis factor
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- Received October 1, 1998.
- Revision received December 7, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
