Possible Involvement of Proteasomes (Prosomes) in AUUUA-mediated mRNA Decay

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-␤ 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.

26S proteasome exhibits endoribonuclease activity controlled by extra-cellular stimuli

“…It has previously been shown that the 20S core proteasomal complex was able to digest single-stranded RNA. [2][3][4][5] However, it was unclear whether the fully assembled 26S complex retained the ability to degrade RNA. To address this question, we decided to examine whether the biochemically purified intact 26S proteasome complex exhibited RNase activity in vitro ( Fig.…”

“…It should be noted, that the same authors demonstrated the inability of 20S core proteasomes to degrade cellular messenger RNA. [2][3][4][5] Thus, it remains unclear whether the 26S proteasome is a large multi-subunit protein complex involved in proteolytic degradation of proteins. In addition to its canonical proteolytic activity, the proteasome is also associated with recently characterized endoribonuclease (endoRNAse) activity.…”

“…Core 20S proteasomes were able to hydrolyze Tobacco Mosaic Virus (TMV) single-stranded RNA and several AU-rich synthetic polyribonucleotides, [2][3][4][5] but not other RNA substrates. These results argue for the specificity of proteasome-mediated endo-RNAse activity.…”

Cytoskeleton-Associated Large RNP Complexes in Tobacco Male Gametophyte (EPPs) Are Associated with Ribosomes and Are Involved in Protein Synthesis, Processing, and Localization

“…[51][52][53] Moreover, a number of transcripts encoding proteasome-associated and F-box proteins were identified in Arabidopsis developing and germinating pollen. 42,54 Proteasomes were also demonstrated to perform other nonproteolytic functions including transcriptional regulation, [55][56][57] RNase activity, 58,59 translational regulation, 60,61 and possessing cytoskeleton-binding properties. 52,62 With regard to all abovementioned alternative functions, the presence of proteasome subunits within EPP complexes is natural in relation to complex EPP-associated spatially and temporarily regulated activities.…”

Elevated Endothelin-1 Expression in Dogs with Heartworm Disease

“…Three copies of the consensus sequence, ATTTA, are present at positions 1661-1665, 1677-1681, and 1790-1794. This motif, which also is found in human PPET-1 cDNA [10], is proposed to mediate selective translationdependent destabilization of mRNA, as was demonstrated for cytokine genes [5,8,13]. Structural analysis of the deduced prepropolypeptide demonstrates that regions corresponding to a bioactive mature ET-1 peptide (C 53 -W 73 ), an intermediate form big ET-1 (C 53 -S 91 ), and an endothelinlike (ET-like) peptide (C 110 -Q 125 ) are found on the deduced polypeptide, as they are in other mammals including humans [9], mice [16], rats [24], and pigs [33].…”