The SKI complex is a cytoplasmic complex composed of a putative RNA helicase (Ski2p), a tetratricopeptide repeat protein (Ski3p) and a WD repeat protein (Ski8p) (8 and references therein). Along with the adaptor protein Ski7p, the SKI complex mediates the cytoplasmic functions of the exosome, a 3'-5' exonuclease complex (3, 4). Together, the SKI complex, Ski7p and the exosome function in a wide range of 3'-5' RNA catabolic processes that include the routine turnover of normal mRNAs (9), the degradation of aberrant mRNAs by 3'-5' nonsense-mediated decay (10) and non-stop mRNA decay (5), and the degradation of other cytoplasmic RNAs including unadenylated RNAs (11) and viral dsRNA (12, 1). Although the SKI complex was originally described as a heterotrimer containing Ski2p, Ski3p and Ski8p (8, 6), later work provides evidence that it is a heterotetramer containing one subunit each of Ski2p and Ski3p, and two subunits of Ski8p (13).

All members of the SKI complex are found in humans and the human genes for hSKI2 (SKIV2L) and hSKI8 (WDR61) have been identified (14, 15, 16). However, Ski7p is found only in a subset of Saccharomyces species (17); the closely related protein, Hbs1p, is likely to fill the role of Ski7p in other fungi and possibly other eukaryotes (18).

Null mutants of ski2, ski3, ski8 and ski7 have similar phenotypes. All have the superkiller phenotype indicative of increased accumulation or viral dsRNA (19 and references therein), and exhibit synthetic lethality with mutations in genes involved in 5'-3' mRNA decay (9, 3).

Although null mutations in SKI7 virtually phenocopy those of SKI2, SKI3 and SKI8, Ski7p is not a member of the SKI complex (8, 4). Instead, Ski7p is thought to function as a coupling factor between the SKI complex and the exosome. The Ski7p protein contains two domains, an N-terminal domain, and a C-terminal "eRF3-like domain" similar to translation termination factor eRF3 (Sup35p). The N-terminal domain is necessary and sufficient for interaction between the SKI complex and the exosome, and for 3'-5' mRNA degradation (4). The C-terminal eRF3-like domain is dispensable for some Ski7p functions, but is thought to be important in non-stop decay, the process by which mRNAs lacking a termination codon are recognized and degraded. The current model for this process suggests that the Ski7p eRF3-like domain binds to an empty aminoacyl-(RNA-binding) site on the stalled ribosome, and this interaction targets the non-stop mRNA for degradation by concerted action of the SKI complex and the exosome (5).

Last updated: 2009-03-24