Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex

Summary

The RNA exosome complex associates with nuclear and cytoplasmic cofactors to mediate the decay, surveillance, or processing of a wide variety of transcripts. In the cytoplasm, the conserved core of the exosome (Exo ₁₀) functions together with the conserved Ski complex. The interaction of S. cerevisiae Exo ₁₀ and Ski is not direct but requires a bridging cofactor, Ski7. Here, we report the 2.65 Å resolution structure of S. cerevisiae Exo ₁₀ bound to the interacting domain of Ski7. Extensive hydrophobic interactions rationalize the high affinity and stability of this complex, pointing to Ski7 as a constitutive component of the cytosolic exosome. Despite the absence of sequence homology, cytoplasmic Ski7 and nuclear Rrp6 bind Exo ₁₀ using similar surfaces and recognition motifs. Knowledge of the interacting residues in the yeast complexes allowed us to identify a splice variant of human HBS1-Like as a Ski7-like exosome-binding protein, revealing the evolutionary conservation of this cytoplasmic cofactor.

Graphical Abstract

Highlights

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  The yeast exosome binds Ski7 with low nanomolar affinity and extensive interactions

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  The Ski7 exosome-binding domain folds upon recognizing Csl4, Mtr3, and Rrp43 subunits

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  Ski7 and Rrp6 lack sequence homology but form a similar interface with the exosome

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  The exosome interface residues of yeast Ski7 are conserved in human Hbs1L isoform 3

Abstract

Kowalinski et al. (2016) show that the yeast exosome core complex recognizes the cytoplasmic cofactor Ski7 and the nuclear cofactor Rrp6 similarly. Through structural analyses, they identify a splice variant of HSB1-Like as the long-sought Ski7-like exosome binding cofactor in humans.