结构生物学sturcture biology explore-4.pdfVIP

? 2000 Nature America Inc. ? review Musing on the structural organization of the exosome complex Philip Mitchell and David Tollervey The exosome complex of 3′→5′ exoribonucleases functions in both the precise processing of 3′ extended precursor molecules to mature stable RNAs and the complete degradation of other RNAs. Both processing and degradative activities of the exosome depend on additional cofactors, notably the putative RNA helicases Mtr4p and Ski2p. It is not known how these factors regulate exosome function or how the exosome distinguishes RNAs destined for processing events from substrates that are to be completely degraded. Here we review the available data concerning the modes of action of the exosome and relate these to possible structural arrangements for the complex. As no detailed structural data are yet available for the exosome complex, or any of its constituent enzymes, this discussion will rely heavily on rather speculative models. A universal feature of stable RNAs is that they are transcribed as 3′ ing domain similar to that present in the E. coli ribosomal protein .com extended precursor molecules that undergo subsequent process- S1 (S1 RBD). The nuclear exosome includes an additional com- ing events, generally exonuclease digestion, to generate the 3′ end ponent, the 3′→5′ exoribonuclease Rrp6p, which is homologous of the mature molecule. Conversely, RNAs such as cytoplasmic to E. coli RNase D4,6. Strikingly, neither complex has obvious mRNAs, nuclear pre-mRNA and the RNA spacer fragments gen- structural or regulatory subunits. They do, however, include erated during processing reactions can also be shortened from the enzymes with distinctly different activities (Table 1). 3′ end but these molecules