Han Jaeil, van Hoof Ambro
Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 1.212, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 1.212, Houston, TX 77030, USA.
Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 1.212, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 1.212, Houston, TX 77030, USA.
Cell Rep. 2016 Sep 20;16(12):3348-3358. doi: 10.1016/j.celrep.2016.08.059.
The RNA exosome is a 3'-5' ribonuclease complex that is composed of nine core subunits and an essential catalytic subunit, Rrp44. Two distinct conformations of Rrp44 were revealed in previous structural studies, suggesting that Rrp44 may change its conformation to exert its function. In the channeling conformation, (Rrp44(ch)), RNA accesses the active site after traversing the central channel of the RNA exosome, whereas in the other conformation, (Rrp44(da)), RNA gains direct access to the active site. Here, we show that the Rrp44(da) exosome is important for nuclear function of the RNA exosome. Defects caused by disrupting the direct access conformation are distinct from those caused by channel-occluding mutations, indicating specific functions for each conformation. Our genetic analyses provide in vivo evidence that the RNA exosome employs a direct-access route to recruit specific substrates, indicating that the RNA exosome uses alternative conformations to act on different RNA substrates.
RNA外切体是一种3'-5'核糖核酸酶复合物，由九个核心亚基和一个必需的催化亚基Rrp44组成。先前的结构研究揭示了Rrp44的两种不同构象，这表明Rrp44可能会改变其构象以发挥其功能。在通道构象（Rrp44(ch)）中，RNA在穿过RNA外切体的中央通道后进入活性位点，而在另一种构象（Rrp44(da)）中，RNA可直接进入活性位点。在这里，我们表明Rrp44(da)外切体对RNA外切体的核功能很重要。破坏直接进入构象所导致的缺陷与通道阻塞突变所导致的缺陷不同，这表明每种构象都有特定功能。我们的遗传分析提供了体内证据，表明RNA外切体采用直接进入途径来招募特定底物，这表明RNA外切体使用不同构象作用于不同的RNA底物。
