6D6Q

Human nuclear exosome-MTR4 RNA complex - overall reconstruction

Summary for 6D6Q

• Entry DOI: 10.2210/pdb6d6q/pdb
• EMDB information: 7808 7809 7810 7812 7813 7814 7815 7818 7819
• Descriptor: Exosome complex component RRP45, Exosome component 10, Exosome complex exonuclease RRP44, ... (18 entities in total)
• Functional Keywords: rna exosome, rna degradation, ribonuclease, helicase, sf2, rna-protein complex, translocase, nuclear, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 15
• Total formula weight: 639178.81

Authors

Weick, E.-M.,Lima, C.D. (deposition date: 2018-04-22, release date: 2018-06-20, Last modification date: 2024-03-13)

Primary citation

Weick, E.M.,Puno, M.R.,Januszyk, K.,Zinder, J.C.,DiMattia, M.A.,Lima, C.D.
Helicase-Dependent RNA Decay Illuminated by a Cryo-EM Structure of a Human Nuclear RNA Exosome-MTR4 Complex.
Cell, 173:1663-, 2018

PubMed Abstract: The ribonucleolytic RNA exosome interacts with RNA helicases to degrade RNA. To understand how the 3' to 5' Mtr4 helicase engages RNA and the nuclear exosome, we reconstituted 14-subunit Mtr4-containing RNA exosomes from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and human and show that they unwind structured substrates to promote degradation. We loaded a human exosome with an optimized DNA-RNA chimera that stalls MTR4 during unwinding and determined its structure to an overall resolution of 3.45 Å by cryoelectron microscopy (cryo-EM). The structure reveals an RNA-engaged helicase atop the non-catalytic core, with RNA captured within the central channel and DIS3 exoribonuclease active site. MPP6 tethers MTR4 to the exosome through contacts to the RecA domains of MTR4. EXOSC10 remains bound to the core, but its catalytic module and cofactor C1D are displaced by RNA-engaged MTR4. Competition for the exosome core may ensure that RNA is committed to degradation by DIS3 when engaged by MTR4.

PubMed: 29906447
DOI: 10.1016/j.cell.2018.05.041

Experimental method

ELECTRON MICROSCOPY (3.45 Å)