Nuclear RNA exosome at 3.1 Å reveals substrate specificities, RNA paths, and allosteric inhibition of Rrp44/Dis3 Journal Article
| Authors: | Zinder, J. C.; Wasmuth, E. V.; Lima, C. D. |
| Article Title: | Nuclear RNA exosome at 3.1 Å reveals substrate specificities, RNA paths, and allosteric inhibition of Rrp44/Dis3 |
| Abstract: | The eukaryotic RNA exosome is an essential and conserved 3′-to-5′ exoribonuclease complex that degrades or processes nearly every class of cellular RNA. The nuclear RNA exosome includes a 9-subunit non-catalytic core that binds Rrp44 (Dis3) and Rrp6 subunits to modulate their processive and distributive 3′-to-5′ exoribonuclease activities, respectively. Here we utilize an engineered RNA with two 3′ ends to obtain a crystal structure of an 11-subunit nuclear exosome bound to RNA at 3.1 Å. The structure reveals an extended RNA path to Rrp6 that penetrates into the non-catalytic core; contacts between the non-catalytic core and Rrp44, which inhibit exoribonuclease activity; and features of the Rrp44 exoribonuclease site that support its ability to degrade 3′ phosphate RNA substrates. Using reconstituted exosome complexes, we show that 3′ phosphate RNA is not a substrate for Rrp6 but is readily degraded by Rrp44 in the nuclear exosome. © 2016 Elsevier Inc. |
| Keywords: | rna; x-ray crystallography; click chemistry; nuclear; structure; exosome; exoribonuclease; multi-subunit complex; rna decay |
| Journal Title: | Molecular Cell |
| Volume: | 64 |
| Issue: | 4 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2016-11-17 |
| Start Page: | 734 |
| End Page: | 745 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2016.09.038 |
| PROVIDER: | scopus |
| PMCID: | PMC5115963 |
| PUBMED: | 27818140 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 6 December 2016 -- Source: Scopus |
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