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Mol Cell. 2016 Nov 17;64(4):734-745. doi: 10.1016/j.molcel.2016.09.038. Epub 2016 Nov 3.

Nuclear RNA Exosome at 3.1 Å Reveals Substrate Specificities, RNA Paths, and Allosteric Inhibition of Rrp44/Dis3.

Author information

1
Tri-Institutional Training Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Structural Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
2
Structural Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
3
Structural Biology Program, Sloan Kettering Institute, 1275 York Avenue, New York, NY 10065, USA; Howard Hughes Medical Institute, 1275 York Avenue, New York, NY 10065, USA. Electronic address: limac@mskcc.org.

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.

KEYWORDS:

RNA; RNA decay; X-ray crystallography; click chemistry; exoribonuclease; exosome; multi-subunit complex; nuclear; structure

PMID:
27818140
PMCID:
PMC5115963
DOI:
10.1016/j.molcel.2016.09.038
[Indexed for MEDLINE]
Free PMC Article

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