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J Biol Chem, Vol. 274, Issue 9, 5925-5930, February 26, 1999

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, Université Blaise 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

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- mRNA that contains AUUUA sequences. We furthermore demonstrate that 20 S proteasomes destabilize oligoribonucleotides corresponding to the 3'-untranslated region of tumor necrosis factor-, 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.

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