7S7B

Human Nuclear exosome targeting (NEXT) complex homodimer bound to RNA (substrate 1)

Summary for 7S7B

• Entry DOI: 10.2210/pdb7s7b/pdb
• EMDB information: 24882
• Descriptor: Exosome RNA helicase MTR4, Zinc finger CCHC domain-containing protein 8,Zinc finger CCHC domain-containing protein 8, RNA-binding protein 7, ... (5 entities in total)
• Functional Keywords: helicase, atpase, rna, exosome, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 423237.96

Authors

Puno, M.R.,Lima, C.D. (deposition date: 2021-09-15, release date: 2022-06-15, Last modification date: 2024-06-05)

Primary citation

Puno, M.R.,Lima, C.D.
Structural basis for RNA surveillance by the human nuclear exosome targeting (NEXT) complex.
Cell, 185:2132-2147.e26, 2022

PubMed Abstract: RNA quality control relies on co-factors and adaptors to identify and prepare substrates for degradation by ribonucleases such as the 3' to 5' ribonucleolytic RNA exosome. Here, we determined cryogenic electron microscopy structures of human nuclear exosome targeting (NEXT) complexes bound to RNA that reveal mechanistic insights to substrate recognition and early steps that precede RNA handover to the exosome. The structures illuminate ZCCHC8 as a scaffold, mediating homodimerization while embracing the MTR4 helicase and flexibly anchoring RBM7 to the helicase core. All three subunits collaborate to bind the RNA, with RBM7 and ZCCHC8 surveying sequences upstream of the 3' end to facilitate RNA capture by MTR4. ZCCHC8 obscures MTR4 surfaces important for RNA binding and extrusion as well as MPP6-dependent recruitment and docking onto the RNA exosome core, interactions that contribute to RNA surveillance by coordinating RNA capture, translocation, and extrusion from the helicase to the exosome for decay.

PubMed: 35688134
DOI: 10.1016/j.cell.2022.04.016

Experimental method

ELECTRON MICROSCOPY (4.06 Å)