| 1997 |
Rrp42p (yeast ortholog of EXOSC7) is an essential component of the yeast exosome, a multi-subunit 3'→5' exoribonuclease complex required for 3' processing of 5.8S rRNA. Rrp42p shares homology with bacterial RNase PH phosphorolytic ribonucleases. |
Mass spectrometry-based complex purification, genetic depletion, in vitro exoribonuclease assays |
Cell |
High |
9390555
|
| 2002 |
Human hRrp42p (EXOSC7) is a genuine component of the human exosome complex. hCsl4p directly interacts with hRrp42p as demonstrated by mammalian two-hybrid and GST pull-down assays, and this interaction mediates hCsl4p association with the exosome in vivo. |
Co-immunoprecipitation, mammalian two-hybrid assay, GST pull-down |
Journal of molecular biology |
Medium |
11812149
|
| 2001 |
Human hRrp42p (EXOSC7) is an autoantigenic component of the PM/Scl complex (human exosome), recognized by autoantibodies in patients with idiopathic inflammatory myopathy, and is one of the most frequently targeted exosome components by autoantibodies. |
ELISA and western blotting using affinity-purified recombinant hRrp42p protein with patient sera |
Arthritis research |
Medium |
11879549
|
| 2005 |
In the archaeal exosome, the Rrp41-Rrp42 heterodimer forms a hexameric ring (three heterodimers). Rrp42 adopts the RNase PH fold but is catalytically inactive; it contributes to structuring the active site of the adjacent catalytic Rrp41 subunit. Structure-guided mutagenesis confirmed that catalytic activity resides exclusively in Rrp41. |
X-ray crystallography at 2.8 Å resolution, structure-guided mutagenesis, in vitro ribonuclease assay |
Nature structural & molecular biology |
High |
15951817
|
| 2005 |
Crystal structures of the Rrp41-Rrp42 core bound to short single-stranded RNAs and ADP revealed: the RNA-binding cleft recognizes four nucleotides in a sequence-unspecific manner primarily via phosphate backbone interactions; 2'-OH specificity distinguishes RNA from DNA; structures of both bound substrate and cleaved product defined the catalytic mechanism of 3'→5' phosphorolytic activity. |
X-ray crystallography with RNA and ADP ligands |
Molecular cell |
High |
16285928
|
| 2007 |
The nine-subunit archaeal exosome channels RNA through a central pore; RNA binds at the active site on one side and at the narrowest constriction of the central channel on the opposite side. This entrapment in the channel provides a mechanistic basis for processive degradation of extended RNAs and stalling at structured RNAs. |
X-ray crystallography at 1.6 Å (apo) and 2.3 Å (RNA-bound) resolution |
EMBO reports |
High |
17380186
|
| 2008 |
Structural studies of the Pyrococcus abyssi RNase PH ring revealed that residues from all three Rrp41-Rrp42 heterodimers contact a single RNA molecule within the catalytic chamber, providing mechanistic evidence for the functional role of the ring assembly in RNA processivity. An ADP-bound structure demonstrated rearrangement at the N1 site, suggesting a mechanism for nucleoside diphosphate elimination after catalysis. |
High-resolution X-ray crystallography, RNA degradation assays with active-site mutants |
The Journal of biological chemistry |
High |
18353775
|
| 2006 |
The catalytic activity of the archaeal exosome resides in the Rrp41-Rrp42 hexameric ring, which degrades RNA phosphorolytically. Rrp4 and Csl4 cap subunits do not exhibit hydrolytic RNase activity alone or in complex, but modulate exosome activity. Various reconstituted complexes of different compositions showed variations in RNase activity, indicating functional interdependence of subunits. |
Biochemical fractionation, reconstitution of defined subcomplexes, RNase activity assays with depleted extracts |
Molecular microbiology |
High |
17078816
|
| 2016 |
The quaternary (hexameric barrel) structure of the archaeal Rrp41:Rrp42 exosome is required for efficient RNA degradation. The entrance pore of the barrel provides nM substrate affinity essential for processivity, preventing premature RNA release. NMR analysis showed the RNA 3' end remains flexible inside the lumen, jumping between three active sites; because jumping is much faster than cleavage, confinement within the lumen ensures continuous active-site engagement. |
Methyl TROSY NMR, in vitro RNA degradation assays, mutagenesis of pore residues |
Nucleic acids research |
High |
26837575
|
| 2025 |
In mammalian cells, EXOSC7 is one of the earliest initiating subunits in RNA exosome assembly; along with EXOSC2 and EXOSC4, it initiates complex formation and facilitates incorporation of barrel and cap subunits in a defined hierarchical order. Orphan (unassembled) EXOSC7 is degraded via the ubiquitin-proteasome system. Disease-associated variants of EXOSC7 show functional defects in yeast complementation assays, with some variants causing reduced protein levels and others being expressed normally yet functionally defective. |
Inducible dual-guide CRISPR/Cas9 KO in mouse embryonic stem cells, humanized yeast complementation, proteasome inhibitor experiments, mass spectrometry |
bioRxivpreprint |
Medium |
39982806
|
| 2025 |
Humanized yeast expressing human EXOSC7 in place of the yeast ortholog revealed that disease-associated patient variants of EXOSC7 cause functional defects. Some patient-derived EXOSC7 variants show reduced protein levels, while others are expressed normally but are functionally impaired, suggesting direct contribution of those residues to RNA exosome function rather than destabilization. |
Humanized yeast complementation (replacement of yeast Rrp42 with human EXOSC7), growth assays, protein level quantification |
G3 (Bethesda, Md.) |
Medium |
39982806
|
| 2023 |
EXOSC7-containing exosome complex is recruited to a ZNF692-organized nucleolar hub specialized in 18S rRNA processing and 40S ribosomal subunit maturation in the granular component of the nucleolus. |
Co-immunoprecipitation, proximity labeling, fluorescence microscopy, KD with ribosome biogenesis functional readout |
Cell reports |
Low |
37851577
|