Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex

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 (Exo10) functions together with the conserved Ski complex. The interaction of S. cerevisia...

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Veröffentlicht in:Molecular cell 2016-07, Vol.63 (1), p.125-134
Hauptverfasser: Kowalinski, Eva, Kögel, Alexander, Ebert, Judith, Reichelt, Peter, Stegmann, Elisabeth, Habermann, Bianca, Conti, Elena
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Sprache:eng
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Zusammenfassung: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 (Exo10) functions together with the conserved Ski complex. The interaction of S. cerevisiae Exo10 and Ski is not direct but requires a bridging cofactor, Ski7. Here, we report the 2.65 Å resolution structure of S. cerevisiae Exo10 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 Exo10 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. [Display omitted] •The yeast exosome binds Ski7 with low nanomolar affinity and extensive interactions•The Ski7 exosome-binding domain folds upon recognizing Csl4, Mtr3, and Rrp43 subunits•Ski7 and Rrp6 lack sequence homology but form a similar interface with the exosome•The exosome interface residues of yeast Ski7 are conserved in human Hbs1L isoform 3 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.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2016.05.028