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Nuclear RNA Exosome at 3.1 A 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.

SUBMITTER: Zinder JC

PROVIDER: S-EPMC5115963 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Zinder John C JC Wasmuth Elizabeth V EV Lima Christopher D CD

Molecular cell 20161103 4

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 str ...[more]

PMID: 27818140

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