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Elife. 2018 Jul 26;7. pii: e38686. doi: 10.7554/eLife.38686.

Distinct and evolutionary conserved structural features of the human nuclear exosome complex.

Author information

1
Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Munich, Germany.
#
Contributed equally

Abstract

The nuclear RNA exosome complex mediates the processing of structured RNAs and the decay of aberrant non-coding RNAs, an important function particularly in human cells. Most mechanistic studies to date have focused on the yeast system. Here, we reconstituted and studied the properties of a recombinant 14-subunit human nuclear exosome complex. In biochemical assays, the human exosome embeds a longer RNA channel than its yeast counterpart. The 3.8 Å resolution cryo-EM structure of the core complex bound to a single-stranded RNA reveals that the RNA channel path is formed by two distinct features of the hDIS3 exoribonuclease: an open conformation and a domain organization more similar to bacterial RNase II than to yeast Rrp44. The cryo-EM structure of the holo-complex shows how obligate nuclear cofactors position the hMTR4 helicase at the entrance of the core complex, suggesting a striking structural conservation from lower to higher eukaryotes.

KEYWORDS:

RNA decay; biochemistry; chemical biology; cryoEM; hDIS3; hEXO-14; hMTR4; human; molecular biophysics; nuclear exosome; structural biology

PMID:
30047866
PMCID:
PMC6072439
DOI:
10.7554/eLife.38686
[Indexed for MEDLINE]
Free PMC Article

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