Mechanistic insights into RNA decay
Eukaryotic cells determine protein abundance in time and space by regulating RNA stability. RNA degradation is now an established mechanism for regulating gene expression during development and differentiation. Although many elements of the RNA decay machinery have been identified, details regarding their function remain elusive. The exosome is a multi-subunit exonuclease complex that degrades many RNA species. Accessory proteins and subcellular localisation determine its substrate preference. Scientists on the EU-funded EXOSOME-SKI-COMPLEX (Structural and functional studies on how the Ski complex activates the exosome to degrade RNA) project wished to elucidate the mechanisms of this mRNA degradation system. For this purpose, they used yeast as a model organism where the Ski complex is the major accessory factor of the cytosolic exosome. The core Ski complex comprises the RNA helicase Ski2, the large protein Ski3 and two copies of Ski8. The protein Ski7 acts as adaptor between exosome and Ski complex. Project researchers obtained several crystal structures and gained structural information around the entire molecule of Ski7. This led them to conclude that the N-terminus of Ski7 is tightly wrapped around the exosome to link it to the Ski complex. The C-terminus of the protein binds GTP and might have a function at the ribosome, similar to translational GTPases. Furthermore, they discovered that the Ski complex had a co-translational function by directly binding to the ribosome. Taken together, the observations made during the EXOSOME-SKI-COMPLEX project provide fundamental insight into the molecular mechanism of RNA degradation. Delineation of the interactions at the atomic level will help interfere with RNA decay in the future to manipulate protein expression for therapeutic purposes.
Keywords
RNA, degradation, exosome, yeast, Ski7
