Possible involvement of proteasomes (prosomes) in AUUUA-mediated mRNA decay

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 leuke mia virus-infected mouse spleen cells were found to be associated with a mR NA fragment showing great homology to the 3'-untranslated region of tumor n ecrosis factor-beta mRNA that contains AUUUA sequences. We furthermore demo nstrate that 20 S proteasomes destabilize oligoribonucleotides correspondin g to the 3'-untranslated region of tumor necrosis factor-alpha, creating a specific cleavage pattern. The cleavage reaction is accelerated with increa sing 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 proteas omes could be involved in the destabilization of cytokine mRNAs such as tum or necrosis factor mRNAs and other short-lived mRNAs containing AUUUA seque nces.