RNA-quality control by the exosome

Abstract

The processing and degradation of RNA sequences is ubiquitous, and these activities can be separated into different classes on the basis of their mechanism and function. The clearest functional differences exist between RNA maturation that will generate a usable RNA from its precursor and RNA degradation that will destroy the RNA completely. There is mounting evidence that all RNA-maturation pathways in eukaryotes are continuously monitored by surveillance systems. A key component of the RNA-surveillance machinery is the exosome complex of 3′→5′ exonucleases. On different substrates this complex is responsible for either total RNA degradation or accurate RNA processing, implying a precise distinction between different classes of substrate. Despite the presence of multiple catalytic sites, the purified yeast exosome is almost entirely inactive. However, several activating cofactors have recently been identified. The role of polyadenylation in eukaryotic cells seems different on either side of the nuclear envelope. The long poly(A) tails on cytoplasmic mRNAs promote stability and translation. By contrast, defective nuclear RNAs are identified and 'tagged' with short oligo(A) tails by the TRAMP polyadenylation complex prior to degradation by the exosome. Such tagging of RNAs by polyadenylation could be conceptually similar to the role of polyubiquitylation in targeting proteins for degradation by the proteasome complex. Key features of RNA degradation have been conserved throughout evolution. Recent structural analyses indicate that the eukaryotic exosome resembles a complex between bacterial PNPase and RNase II, the most active degradative exonucleases in Escherichia coli lysates. Moreover, the role of eukaryotic poly(A) polymerases in targeting nuclear RNAs for degradation is strikingly similar to the role of oligoadenylation in stimulating RNA degradation in bacteria.