Archaeal Rrp4 Exosomes
Archaeoglobus fulgidus (archaea)
RNA plays various roles in biological processes after having been transcripted from DNA. While mRNA is translated into protein, other RNAs such as tRNA, rRNA, and ribozyme themselves work functionally. The RNAs have to be processed to become mature RNAs. The exosome was first identified as a large multisubunit RNase complex which processes rRNA in yeast. Subsequent work identified similar exosomes in archaea and eukaryotes. Functional analysis revealed that exosomes are involved in many other RNA processing or degradation pathways. However, the structural mechanism of exosomes in diverse and selective RNA processing and degradation pathway is still poorly understood.
Buttner et al. reported the crystal structure of nonameric exosome in archaea. The exosome described here is named "Rrp4 exosome" because of its identical subunit, Rrp4. Rrp4 forms flat, trimeric multidomain caps that cover the top face of the Rrp41-Rrp42 complex. Rrp41 and Rrp42 subunits assemble into a hexametric ring, which is called RNase PH domain. RNase PH domain contains a neck (about 10 angstrom pore) and a 3'-5' phosphorolytic active site. The anomalous dispersion data by tungstate, which mimics phosphate, revealed that acidic residues in the Rrp41 pocket at the interface between Rrp41 and Rrp42 are the center of phosphorolytic activity, and the bottom of RNase PH domain forms a pore which leads to the phospho rolytic active site. However, archaeal Rrp4 exosomes do not possess RNase activity in vitro while Arabidosis and yeast Rrp4 exosomes do. Wherefrom the difference derives is still unclear. Rrp4 contains three domains, N-terminal(NT), S1, and KH. The hydrophobic surface of these domains interacts with the hydrophobic surfaces of Rrp41 and Rrp42, which results in the nonameric structure. Rrp4 is considered to be a large platform that recruits RNA substrates and cofactors because of its positive surface potential. Typically, the S1 pore is a good candidate for the RNA binding site because it has the strongest positive potential in Rrp4. The results suggest the RNA degradation mechanism of exosomes. At first, RNA binds to the surface of Rrp4. Then the RNA reaches the phosphorolytic active site via the S1 pore and neck. The pore in the neck is so small that RNA needs to be completely unfolded. In the active site, the 3' region of the RNA is degraded and the degraded fragments exit from the bottom pore. This framework can be a good model for not only the RNA degradation mechanism of eukaryote exosomes, but also the protein degradation mechanism of proteasomes.
Protein Data Bank (PDB)
author: Daisuke Ino