Structure of an Rrp6-RNA exosome complex bound to poly(A) RNA

摘要

外来体复合物包含两个催化亚单元,它们以分布式(Rrp6)或进行式(Rrp44)降解RNA。以前的结构显示了RNA怎样被引导到Rrp44上,但引导到RrP6的路径却不清楚。现在,Christopher Lima及同事解决了酵母的一个由十个亚单元组成(缺少Rrp44)、与单链RNA相结合的外来体复合物的晶体结构。Rrp6催化域的位置及RNA 3'端被确定,但更重要的是,RNA取向被发现与来自含Rrp44的外来体复合物结构的RNA取向相反。这一结果表明,一个RNA的命运可能是根据这个RNA怎样结合到该复合物上所做出的一个随机决定。%The eukaryotic RNA exosome processes and degrades RNA by directing substrates to the distributive or processive 3' to 5' exoribonuclease activities of Rrp6 or Rrp44, respectively. The non-catalytic nine-subunit exosome core (Exo9) features a prominent central channel. Although RNA can pass through the channel to engage Rrp44, it is not clear how RNA is directed to Rrp6 or whether Rrp6 uses the central channel. Here we report a 3.3 A crystal structure of a ten-subunit RNA exosome complex from Saccharomyces cerevisiae composed of the Exo9 core and Rrp6 bound to single-stranded poly(A) RNA. The Rrp6 catalytic domain rests on top of the Exo9 S1/KH ring above the central channel, the RNA 3' end is anchored in the Rrp6 active site, and the remaining RNA traverses the S1/KH ring in an opposite orientation to that observed in a structure of a Rrp44-containing exosome complex. Solution studies with human and yeast RNA exosome complexes suggest that the RNA path to Rrp6 is conserved and dependent on the integrity of the S1/KH ring. Although path selection to Rrp6 or Rrp44 is stochastic in vitro, the fate of a particular RNA may be determined in vivo by the manner in which cofactors present RNA to the RNA exosome.