Untitled

Abstract

The 20S proteasome (prosome) is a highly organized multiprotein complex with approximate molecular weight of about 700 kDa. Whilst the role of the proteasome in the processing and turnover of cellular proteins is becoming clearer, its relationship with RNA remains still obscure. Here we focus on the nature and function of proteasome associated endonuclease activity. Thus the involvement of a proteasome alpha-type subunit in RNA-degradation, the catalytic requirements, the interaction of proteasomes with their RNA-substrate and the identification of a well defined cleavage site in the 3'UTR of short-lived cellular mRNAs will be described in detail. All data indicate that proteasomes associated endonuclease activity could be involved in post-transcriptional gene control at the level of translation.

DNA damage modulates interactions between microRNAs and the 26S proteasome

“…In fact, the abundance of the RNA fraction associated with proteasomes was calculated and varied from 0.0016% up tо 0.2% of total RNA depending on the organism and specific tissue used for experiments [30]. We wanted to test whether genotoxic stress, known to regulate both proteolytic and RNAse activities of proteasomes, also affected the binding of RNA to proteasomes.…”

“…That proteasomal 20S particles were associated with low molecular weight (lmw) RNA species has been known for decades [19, 20, 28, 30]. However, neither the exact composition nor the function(s) of these lmw RNAs were characterised in details.…”

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

“…eration of degradation of ARE containing messengers. Others described a 32-kDa protein identical to HuR that specifically cross-links to (AUUUA) 4 and (AUUUUA) 3 but not (AUA) 8 and (AUUA) 5 RNAs in vitro (30). This protein would play an RNAstabilizing role in the ARE-directed mRNA decay in mammalian cells (31).…”

“…3C shows typical profiles of proteasome-associated RNAs, which migrate as a heterogeneous population ranging from 60 to 500 nucleotides. Highly purified proteasomes washed with 1% lauroylsarkosyl contain almost one RNA species, which was identified to be tRNA Lys3 (3,25). For sequencing, RNAs were extracted from less purified 20 S fractions.…”

“…Thus, it is involved in the regulation of transcription, antigen presentation, and the degradation of damaged and misfolded proteins, and it drives the cell cycle (1). In addition, there is evidence for the involvement of the proteasome in post-transcriptional control of gene expression (2,3).…”