Razew Michal, Warkocki Zbigniew, Taube Michal, Kolondra Adam, Czarnocki-Cieciura Mariusz, Nowak Elzbieta, Labedzka-Dmoch Karolina, Kawinska Aleksandra, Piatkowski Jakub, Golik Pawel, Kozak Maciej, Dziembowski Andrzej, Nowotny Marcin
Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109, Warsaw, Poland.
Laboratory of RNA Biology and Functional Genomics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106, Warsaw, Poland.
Nat Commun. 2018 Jan 8;9(1):97. doi: 10.1038/s41467-017-02570-5.
Nuclease and helicase activities play pivotal roles in various aspects of RNA processing and degradation. These two activities are often present in multi-subunit complexes from nucleic acid metabolism. In the mitochondrial exoribonuclease complex (mtEXO) both enzymatic activities are tightly coupled making it an excellent minimal system to study helicase-exoribonuclease coordination. mtEXO is composed of Dss1 3'-to-5' exoribonuclease and Suv3 helicase. It is the master regulator of mitochondrial gene expression in yeast. Here, we present the structure of mtEXO and a description of its mechanism of action. The crystal structure of Dss1 reveals domains that are responsible for interactions with Suv3. Importantly, these interactions are compatible with the conformational changes of Suv3 domains during the helicase cycle. We demonstrate that mtEXO is an intimate complex which forms an RNA-binding channel spanning its entire structure, with Suv3 helicase feeding the 3' end of the RNA toward the active site of Dss1.
核酸酶和解旋酶活性在RNA加工和降解的各个方面发挥着关键作用。这两种活性通常存在于核酸代谢的多亚基复合物中。在线粒体外切核糖核酸酶复合物（mtEXO）中，这两种酶活性紧密耦合，使其成为研究解旋酶-外切核糖核酸酶协同作用的极佳最小系统。mtEXO由Dss1 3'-至-5'外切核糖核酸酶和Suv3解旋酶组成。它是酵母中线粒体基因表达的主要调节因子。在这里，我们展示了mtEXO的结构及其作用机制的描述。Dss1的晶体结构揭示了负责与Suv3相互作用的结构域。重要的是，这些相互作用与解旋酶循环期间Suv3结构域的构象变化相容。我们证明mtEXO是一种紧密的复合物，形成一个贯穿其整个结构的RNA结合通道，Suv3解旋酶将RNA的3'末端输送到Dss1的活性位点。
