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Showing EXOSC10 — RRP6 is a alias.

EXOSC10

Exosome complex component 10 · UniProt Q01780

Length
885 aa
Mass
100.8 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EXOSC10 (PM-Scl100/Rrp6) is the nuclear-specific, distributive 3'-to-5' exoribonuclease subunit of the RNA exosome that surveils and matures nuclear RNAs, and it is biochemically restricted to the nuclear form of the complex while absent from the cytoplasmic form (PMID:10465791, PMID:1644924). It is an RNase D-type enzyme that uses a two-metal-ion catalytic mechanism: mutation of conserved metal-coordinating active-site residues abolishes both in vitro and in vivo exonuclease activity, and its flanking HRDC domain selectively governs processing (5.8S rRNA, snoRNA 3'-end maturation) independently of bulk degradation (PMID:9582370, PMID:16882719, PMID:12923258). Acute depletion defines its principal physiological substrates as short 3'-extended ribosomal RNAs and snoRNAs, distinguishing it from the DIS3 catalytic subunit, which acts on enhancer RNAs and PROMPTs (PMID:30840897). Within the holoenzyme, EXOSC10 rests atop the Exo9 S1/KH ring with the substrate 3' end threaded into its active site, and its catalytic output is tuned by partner proteins and an internal basic 'lasso' tail (PMID:25043052, PMID:27899565). Through its N-terminal PMC2NT domain it forms an intertwined unit with Rrp47/C1D and recruits the Mtr4/TRAMP machinery, which directly stimulates its hydrolytic activity ~10-fold; together these cofactors are required for efficient pre-rRNA 3'-end processing (PMID:17412707, PMID:17704127, PMID:19955569, PMID:25319414). EXOSC10 activity is post-translationally controlled by SUMO1 conjugation, including a cooling-responsive modification and USP36-mediated SUMOylation at lysine 583 that promotes pre-rRNA binding and ribosome biogenesis (PMID:26857222, PMID:36912080). Beyond RNA surveillance, EXOSC10 is recruited to DNA double-strand breaks where its ribonucleolytic activity clears damage-induced lncRNAs and DNA-RNA hybrids to enable RPA loading, RAD51 recruitment, and controlled end resection for homologous recombination (PMID:25632158, PMID:31086179). Genetic ablation in mouse germ cells and oocytes establishes essential roles in gametogenesis and meiotic maturation, where it sculpts the transcriptome to permit CDK1 activation, germinal vesicle breakdown, and proper germ cell differentiation (PMID:32313933, PMID:29118343).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1992 Medium

    Molecular identification of the PM-Scl 100-kD autoantigen as a distinct nuclear protein established the gene product and its nucleolar localization, providing the entry point for all later mechanistic work.

    Evidence cDNA cloning with affinity-purified antibody immunofluorescence and immunoprecipitation in HEp-2 cells

    PMID:1644924

    Open questions at the time
    • No enzymatic activity assigned
    • No exosome association established at this stage
  2. 1998 High

    Identifying yeast Rrp6 as an RNase D-homologous 3'-5' exoribonuclease required for 5.8S rRNA 3'-end formation defined the core catalytic function of the gene family.

    Evidence Genetic selection, cloning, and pulse-chase RNA analysis in yeast

    PMID:9582370

    Open questions at the time
    • Catalytic mechanism not yet resolved at atomic level
    • Human ortholog activity not yet demonstrated
  3. 1999 High

    Demonstrating that EXOSC10 is present only in the nuclear exosome and not the cytoplasmic form, and that it joins the nucleolus late during mitotic reassembly, anchored its compartment-specific role in nuclear RNA metabolism.

    Evidence Biochemical fractionation, immunofluorescence, and antibody microinjection time-course in yeast and human cells

    PMID:10465791 PMID:10471330

    Open questions at the time
    • Mechanism of nuclear retention not defined
    • Order of nucleolar targeting cues unresolved
  4. 2006 High

    Crystallography and active-site mutagenesis established the two-metal-ion catalytic mechanism and showed the HRDC domain conformation specifically controls processing versus degradation, revealing independently regulated activities.

    Evidence X-ray crystallography of yeast Rrp6 with AMP/UMP plus in vivo and in vitro mutagenesis

    PMID:12923258 PMID:16882719

    Open questions at the time
    • Structural basis of HRDC conformational switching not defined
    • Human enzyme structure not yet solved
  5. 2007 High

    Mapping of cofactor interfaces showed EXOSC10 binds C1D/Rrp47 and MPP6 and engages Mtr4 through its N-terminal PMC2NT domain, with these cofactors required for efficient rRNA processing, defining the recruitment architecture.

    Evidence Co-IP, in vitro reconstitution, pull-down domain mapping, and RNAi in human and yeast systems

    PMID:17412707 PMID:17704127

    Open questions at the time
    • Quantitative contribution of each cofactor to catalysis not separated
    • Substrate handoff dynamics unresolved
  6. 2008 High

    Showing that a core-exosome-untethered Rrp6 retains certain processing and degradation activities while others require the core established that EXOSC10 has both exosome-dependent and -independent functions.

    Evidence C-terminal truncation, affinity purification, and genetic epistasis in yeast

    PMID:18940861

    Open questions at the time
    • Which substrates strictly require core association not fully enumerated
    • In vivo relevance of free Rrp6 pool unclear
  7. 2009 High

    Demonstrating TRAMP directly stimulates Rrp6 hydrolytic activity ~10-fold independently of its polymerase/helicase activities revealed allosteric activation of the catalytic subunit by its recruitment machinery.

    Evidence In vitro exonuclease assays with purified components and active-site mutagenesis

    PMID:19955569

    Open questions at the time
    • Structural basis of stimulation not resolved
    • Whether human TRAMP confers identical stimulation untested here
  8. 2009 Medium

    Drosophila dRrp6's requirement for error-free mitosis independently of the core exosome, with chromosome-associated redistribution, indicated a function beyond canonical RNA processing.

    Evidence RNAi depletion, mitotic imaging, FACS, and spindle checkpoint assays in S2 cells

    PMID:19225159

    Open questions at the time
    • RNA substrate underlying the mitotic role not identified
    • Conservation to mammalian mitosis not established
  9. 2011 High

    The human RRP6 crystal structure showed a more exposed active site than yeast, correlating with enhanced ability to degrade structured RNA, distinguishing the human enzyme's substrate range.

    Evidence X-ray crystallography of human RRP6 exo+HRDC construct and comparative in vitro assays

    PMID:21705430

    Open questions at the time
    • Full-length human enzyme structure not solved
    • Cellular consequence of structured-RNA preference not mapped
  10. 2012 Medium

    Linking EXOSC10 to Microprocessor/Setx/Xrn2-driven transcription termination and to nuclear mRNP surveillance via Nab2/PABP displacement expanded its role into co-transcriptional regulation and poly(A) control.

    Evidence ChIP-seq, RNAi, transcription termination assays (HIV-1 promoter) and in vitro polyadenylation/Co-IP in yeast

    PMID:22683267 PMID:22980978

    Open questions at the time
    • Generality beyond the HIV-1 model promoter unclear
    • Direct vs indirect role in termination not fully separated
  11. 2014 High

    High-resolution structures placed Rrp6 atop the Exo9 S1/KH ring with RNA threaded through the channel and defined the intertwined Rrp6-Rrp47 surface that captures Mtr4, establishing the structural logic of substrate channeling and helicase recruitment.

    Evidence X-ray crystallography (3.3 Å ten-subunit exosome; Rrp6-Rrp47-Mtr4 interface) with solution biochemistry and mutagenesis

    PMID:25043052 PMID:25319414

    Open questions at the time
    • Conformational changes during catalytic cycling not captured
    • Dynamics of channel threading not time-resolved
  12. 2015 High

    Recruitment of RRP6/EXOSC10 to DNA double-strand breaks and the catalytic requirement for RAD51 loading placed its ribonucleolytic activity directly in the homologous recombination pathway.

    Evidence Immunofluorescence, RNAi, reciprocal Co-IP, and catalytic-mutant rescue in Drosophila and human cells

    PMID:25632158

    Open questions at the time
    • RNA species cleared at breaks not yet identified in this study
    • Recruitment mechanism to DSBs undefined
  13. 2016 Medium

    Identifying SUMO1 conjugation of EXOSC10 (cooling-induced, suppressing abundance) and the stimulatory basic C-terminal lasso established post-translational and intramolecular tuning of its ribosome-biogenesis output.

    Evidence RNAi, SUMO-site mutagenesis, ribosome profiling, and in vitro truncation/RNA-binding assays

    PMID:26857222 PMID:27899565

    Open questions at the time
    • SUMO ligase for cooling-induced modification not identified here
    • Physiological trigger range beyond cooling unknown
  14. 2018 Medium

    Showing two-step trimming of telomerase RNA precursor by RRP6 then PARN, promoted by H/ACA RNP assembly, extended EXOSC10's processing role to a specific non-coding RNA maturation pathway.

    Evidence In vitro processing assays, RNAi, RNA structure analysis, and RNP reconstitution

    PMID:30575725

    Open questions at the time
    • In vivo contribution to functional telomerase levels not quantified
    • Determinants directing processing vs degradation only partly mapped
  15. 2019 High

    Acute degron depletion defined EXOSC10's primary substrates as short 3'-extended rRNAs and snoRNAs, and DSB studies showed it clears dilncRNAs/DNA-RNA hybrids to enable RPA loading and controlled end resection, sharpening both its surveillance specificity and its genome-stability function.

    Evidence Auxin-inducible degron with substrate-binding mapping and RNA-seq; plus RNAi, DRIP, resection assays, and RNase H1 rescue in human cells

    PMID:30840897 PMID:31086179

    Open questions at the time
    • How substrate selectivity is enforced mechanistically not defined
    • Coupling between rRNA-processing and DSB roles unresolved
  16. 2020 High

    Germ-cell and oocyte-specific knockouts established EXOSC10 as essential for gametogenesis and meiotic maturation, sculpting the transcriptome to permit CDK1 activation, germinal vesicle breakdown, and germ cell differentiation.

    Evidence Conditional Cre/CRISPR knockouts in mouse testis and oocytes with single-oocyte RNA-seq, immunofluorescence, and rRNA processing analysis

    PMID:29118343 PMID:32313933

    Open questions at the time
    • Direct vs indirect targets driving meiotic phenotypes not fully separated
    • Whether developmental defects stem chiefly from rRNA vs mRNA roles unclear
  17. 2023 High

    Identifying USP36 as a nucleolar SUMO ligase that SUMOylates EXOSC10 at K583 to promote pre-rRNA binding established a specific functional modification required for ribosome biogenesis.

    Evidence Co-IP, SUMOylation and CLIP/binding assays, K583R mutagenesis, and RNAi rescue in human cells

    PMID:36912080

    Open questions at the time
    • Structural effect of K583 SUMOylation on pre-rRNA engagement undefined
    • Crosstalk with cooling-induced SUMOylation not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EXOSC10 selectively partitions among its distinct roles—nucleolar rRNA/snoRNA maturation, DSB RNA clearance, and meiotic transcriptome sculpting—and how its modifications and cofactors switch between these programs remains unresolved.
  • No unified model of substrate/role partitioning
  • Recruitment determinants to DSBs vs nucleolus undefined
  • Regulatory hierarchy of SUMOylation events unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 5 GO:0003723 RNA binding 3 GO:0016787 hydrolase activity 3
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 3 GO:0005654 nucleoplasm 1
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-1474165 Reproduction 2 R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-73894 DNA Repair 2
Partners
C1DMPP6MTR4NAB2RAD51RRP47USP36
Complex memberships
TRAMP complex (functional partner)nuclear RNA exosome

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 EXOSC10 (PM-Scl100/Rrp6p) is exclusively present in the nuclear form of the exosome complex but absent from the cytoplasmic form, as demonstrated by biochemical fractionation and indirect immunofluorescence in both yeast and human cells. The human PM-Scl complex and yeast exosome are functionally equivalent, with the Rrp4p subunit confirmed as shared between both complexes. Biochemical fractionation, indirect immunofluorescence, genetic complementation Genes & development High 10465791
1998 Yeast Rrp6p (homolog of human PM-Scl100/EXOSC10) is a 3'-5' exoribonuclease (homologous to RNase D) required for 5.8S rRNA 3' end formation; loss-of-function mutations cause accumulation of a 5.8S* processing intermediate retaining ~30 nucleotides of ITS2, with pulse-chase demonstrating a precursor-product relationship between 5.8S* and mature 5.8S rRNA. Genetic selection, molecular cloning, pulse-chase RNA analysis, sequence homology to RNase D The Journal of biological chemistry High 9582370
2006 Crystal structure of yeast Rrp6p reveals a conserved RNase D core with a flanking HRDC domain in an unusual conformation. Complexes with AMP and UMP show how the protein specifically recognizes ribonucleotides. In vivo mutagenesis of conserved active-site residues and the HRDC domain demonstrates that the HRDC domain conformation is important for the processing (but not degradation) function, revealing independent control of processing vs. degradation activities. X-ray crystallography, in vivo mutagenesis, RNA processing assays Proceedings of the National Academy of Sciences of the United States of America High 16882719
2003 Mutation of conserved active-site residues predicted to coordinate metal ions in Rrp6p (yeast homolog of EXOSC10) abolishes in vitro and in vivo exoribonuclease activity, confirming a two-metal ion mechanism. The HRDC domain point mutation results in nuclear-localized Rrp6p that retains degradation activity but loses 5.8S rRNA and snoRNA 3'-end processing activity, demonstrating domain-specific functional separation. Site-directed mutagenesis, in vitro exonuclease assays, in vivo RNA processing assays RNA (New York, N.Y.) High 12923258
2007 Human EXOSC10 (PM/Scl-100) co-localizes with C1D and hMtr4p in nucleoli. C1D binds directly to PM/Scl-100 (EXOSC10), and C1D, MPP6, and PM/Scl-100 form a stable trimeric complex in vitro. The nucleolar accumulation of C1D is dependent on PM/Scl-100. RNAi knockdown of C1D, MPP6, or hMtr4p causes accumulation of 3'-extended 5.8S rRNA precursors, demonstrating these cofactors are required for EXOSC10-dependent rRNA processing. Co-immunoprecipitation, subcellular localization, in vitro reconstitution, RNAi knockdown, Northern blotting Nucleic acids research High 17412707
2007 The PMC2NT domain at the N-terminus of Rrp6p (EXOSC10 homolog) is the binding interface for Rrp47p cofactor, as shown by pull-down assays. Rrp47p binds structured nucleic acids and promotes Rrp6p activity. Strains expressing Rrp6p lacking the N-terminal PMC2NT domain fail to accumulate Rrp47p at normal levels and exhibit RNA processing defects consistent with loss of Rrp47p function. Recombinant protein pull-down, nucleic acid binding assays, in vivo mutagenesis, RNA processing assays Nucleic acids research High 17704127
2008 Rrp6p (EXOSC10 yeast homolog) can perform some RNA 3'-end processing functions (5.8S rRNA, snoRNAs) and degrade specific substrates independently of physical association with the nine-subunit core exosome, as shown by a C-terminal truncation that abolishes core exosome co-purification but retains these activities. However, combined activities of Rrp6p and Dis3p/core exosome are required for efficient degradation of certain poly(A)+ rRNA processing products. Affinity purification, RNA processing assays, genetic epistasis (double depletion), Northern blotting Nucleic acids research High 18940861
2009 The TRAMP complex directly enhances the 3'-5' exoribonuclease activity of purified Rrp6p (EXOSC10 yeast homolog) ~10-fold in vitro, independently of TRAMP's poly(A) polymerase (Trf4) and helicase (Mtr4) activities. Enhancement requires a key catalytic residue in Rrp6p's active site; TRAMP cannot stimulate a catalytically inactive Rrp6p mutant, confirming the effect is on Rrp6p hydrolytic activity specifically. In vitro exonuclease assay with purified recombinant proteins, active-site mutagenesis The Journal of biological chemistry High 19955569
2011 Human RRP6 (EXOSC10/PM-Scl-100) exhibits distributive 3'-to-5' exoribonuclease activity and is inhibited by stable RNA secondary structure. X-ray crystal structure of the human RRP6 exoribonuclease+HRDC domain construct shows a more exposed active site compared to yeast Rrp6, which correlates with human RRP6's greater ability to degrade structured RNA substrates in vitro. X-ray crystallography, in vitro exonuclease assays, comparison of human and yeast constructs RNA (New York, N.Y.) High 21705430
2012 Human EXOSC10 (Rrp6/PM-Scl-100) functions with Microprocessor, Setx, and Xrn2 to induce RNAPII pausing and premature transcription termination at the HIV-1 promoter. EXOSC10 further processes Microprocessor cleavage products to generate small RNAs that mediate transcriptional repression and chromatin remodeling. ChIP-seq identified cellular gene targets modulated by this pathway. ChIP-seq, RNAi knockdown, transcription termination assays, chromatin remodeling assays Cell Medium 22980978
2012 The nuclear exosome subunit Rrp6p (EXOSC10 homolog) counteracts poly(A) tail extension by Trf4p in vitro and in vivo, and controls PABP loading: Rrp6p interacts with Nab2p and displaces it from poly(A) tails, potentially directing RNAs to turnover. This defines a nuclear mRNP surveillance step involving Rrp6p targeting of Nab2p-bound poly(A)-tailed RNPs. In vitro polyadenylation assay, co-immunoprecipitation, RNA-seq, genetic analysis Molecular cell Medium 22683267
2014 Crystal structure of a ten-subunit yeast RNA exosome (Exo9 core + Rrp6) bound to poly(A) RNA at 3.3 Å resolution shows the Rrp6 catalytic domain resting on top of the Exo9 S1/KH ring above the central channel, with the RNA 3' end anchored in the Rrp6 active site. RNA traverses the S1/KH ring in the opposite orientation to Rrp44-bound complexes. Solution studies with human and yeast exosomes confirm the RNA path to Rrp6 is conserved and dependent on S1/KH ring integrity. X-ray crystallography (3.3 Å), solution biochemistry, cross-species validation with human RRP6 Nature High 25043052
2014 The N-terminal domains of Rrp6 and Rrp47 form a highly intertwined structural unit (crystallographic analysis) that creates a composite conserved surface groove binding the N-terminus of Mtr4 helicase. Mtr4 binding to the exosome core (Exo-10) in vitro requires both Rrp6 and Rrp47. Mutation of conserved residues at the Rrp6–Mtr4 interface disrupts their interaction and inhibits yeast growth. X-ray crystallography, in vitro binding assays, site-directed mutagenesis, yeast growth assays The EMBO journal High 25319414
2015 RRP6/EXOSC10 is recruited to DNA double-strand breaks (DSBs) in Drosophila S2 cells (RRP6) and human HeLa cells (EXOSC10). Depletion of RRP6/EXOSC10 impairs RAD51 recruitment to DSBs without affecting H2AX phosphorylation. Catalytically inactive RRP6-Y361A mutant also inhibits RAD51 recruitment, demonstrating that ribonucleolytic activity is required. RRP6/EXOSC10 co-immunoprecipitates with RAD51, placing it in the homologous recombination pathway. Immunofluorescence, RNAi depletion, co-immunoprecipitation, catalytic mutant overexpression, radiation sensitivity assay Journal of cell science High 25632158
2016 The Rrp6 C-terminal 'lasso' domain (highly basic tail) binds RNA and stimulates ribonuclease activities of both Rrp44 and Rrp6 within the 11-subunit nuclear exosome. Stimulation is dependent on the Exo9 central channel. The lasso contributes to degradation and processing of exosome substrates in vitro and in vivo, and is proposed to be a conserved feature. In vitro exonuclease assays, RNA binding assays, truncation mutants, in vivo RNA processing assays Nucleic acids research Medium 27899565
2016 EXOSC10 is SUMOylated (conjugated with SUMO1) in response to cellular cooling in human cells and in vivo. The major SUMOylation sites in EXOSC10 were identified by mutagenesis. Overexpression of SUMO1 alone is sufficient to suppress EXOSC10 abundance. RNAi depletion of EXOSC10 causes 3' pre-rRNA processing defects and reduces the 40S:60S ribosomal subunit ratio, demonstrating that SUMOylation-mediated reduction of EXOSC10 downregulates ribosome biogenesis. RNAi knockdown, site-directed mutagenesis of SUMOylation sites, ribosome profiling, in vivo cooling model RNA (New York, N.Y.) Medium 26857222
2018 EXOSC10 (RRP6) processes 3'-extended forms of human telomerase RNA (hTR) precursor in two steps: longer forms are first trimmed by RRP6 and shorter forms are then processed by PARN. H/ACA RNP assembly on hTR actively promotes RRP6-dependent processing and disrupts tertiary RNA interactions (triplex) in longer precursors that would otherwise favor degradation over productive processing. In vitro processing assays, RNAi knockdown, RNA structure analysis, RNP reconstitution Nature communications Medium 30575725
2019 Depletion of EXOSC10 in human cells leads to increased damage-induced lncRNA (dilncRNA) and DNA-RNA hybrid levels at DNA double-strand breaks. EXOSC10 depletion impairs RPA targeting to damage sites and causes hyper-stimulated DNA end resection. RNase H1 overexpression rescues the RPA recruitment defect, demonstrating that EXOSC10-mediated RNA clearance of dilncRNAs is required for RPA assembly and controlled DNA end resection in homologous recombination. RNAi depletion, immunofluorescence, DNA-RNA hybrid detection (DRIP), DNA end resection assays, RNase H1 rescue Nature communications High 31086179
2019 Rapid depletion of EXOSC10 in human cells reveals that its primary substrates are short 3'-extended ribosomal RNAs and small nucleolar RNAs (snoRNAs), distinct from DIS3 substrates (enhancer RNAs, PROMPTs, PCPA products). Enhancer RNAs and PROMPTs are unaffected by EXOSC10 loss, demonstrating substrate specificity within the nuclear exosome. Auxin-inducible degron rapid depletion, direct EXOSC10 binding substrate mapping, RNA-seq Cell reports High 30840897
2020 Oocyte-specific conditional knockout of Exosc10 in mice causes female subfertility due to delayed germinal vesicle breakdown (GVBD). Single-oocyte RNA-seq reveals dysregulation of mRNAs encoding endomembrane trafficking proteins and meiotic cell cycle regulators. EXOSC10-depleted oocytes show CDK1 activation failure (with persistent WEE1 activity), impaired lamina phosphorylation/disassembly, rRNA processing defects, and endomembrane organelle abnormalities. CRISPR/Cas9 conditional knockout, single oocyte RNA-seq, immunofluorescence, rRNA processing analysis Nucleic acids research High 32313933
2017 EXOSC10 is post-translationally regulated in male germ cells; the protein becomes unstable at later stages of gamete development. EXOSC10 localizes to nucleoli and cytoplasm of mitotic and meiotic germ cells and transiently associates with the XY body (a meiotic sex chromosome inactivation structure). Germ cell-specific knockout using Stra8-Cre or Ddx4/Vasa-Cre results in small testes, impaired germ cell differentiation, and subfertility. Cre-mediated conditional knockout, immunofluorescence, subcellular localization, protein stability analysis Scientific reports High 29118343
2023 The nucleolar ubiquitin-specific protease USP36 directly interacts with EXOSC10 in the nucleolus and acts as a SUMO ligase mediating EXOSC10 SUMOylation at lysine 583. Mutation of K583 impairs EXOSC10 binding to pre-rRNAs. K583R mutant EXOSC10 fails to rescue rRNA processing defects and cell growth inhibition caused by knockdown of endogenous EXOSC10, demonstrating that K583 SUMOylation is functionally required for nucleolar RNA exosome activity in ribosome biogenesis. Co-immunoprecipitation, SUMOylation assays, site-directed mutagenesis (K583R), CLIP/binding assays for pre-rRNA interaction, RNAi rescue experiments Nucleic acids research High 36912080
1999 PM-Scl100/EXOSC10 localizes to prenucleolar bodies (PNBs) that are translocated to the nucleolus later than fibrillarin-containing PNBs at mitosis/interphase transition. Microinjection of anti-PM-Scl100 antibodies during mitosis inhibits targeting of PM-Scl100 to the nucleolus without affecting fibrillarin or protein B23 nucleolar assembly, suggesting an ordered pathway for nucleolar reassembly in which EXOSC10 participates in late events. Antibody microinjection, indirect immunofluorescence time-course, subcellular localization during mitosis Experimental cell research Medium 10471330
1992 The cDNA encoding the PM-Scl 100-kD protein (EXOSC10) was cloned; affinity-purified antibody against the clone product stained nucleoli of HEp-2 cells and immunoprecipitated the PM-Scl protein complex, establishing nuclear/nucleolar localization. The predicted protein sequence (98,088 Da) contains a mixed-charge cluster. No sequence homology was found with PM-Scl 75-kD protein. cDNA cloning, immunoblot, indirect immunofluorescence, immunoprecipitation The Journal of clinical investigation Medium 1644924
2009 Drosophila dRrp6 (EXOSC10 ortholog) is required for cell proliferation and error-free mitosis in S2 cells independently of the core exosome (depletion of core subunit Rrp40 does not cause the same mitotic defects). dRrp6 dynamically redistributes during mitosis, accumulating predominantly on condensed chromosomes, while core exosome subunits localize to microtubules. Depletion causes defects in chromosome congression, separation, and segregation. RNAi depletion, microarray analysis, immunofluorescence during mitosis, FACS analysis, spindle checkpoint assays Molecular biology of the cell Medium 19225159

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 The yeast exosome and human PM-Scl are related complexes of 3' --> 5' exonucleases. Genes & development 390 10465791
1998 Rrp6p, the yeast homologue of the human PM-Scl 100-kDa autoantigen, is essential for efficient 5.8 S rRNA 3' end formation. The Journal of biological chemistry 262 9582370
2016 P4-ATPases as Phospholipid Flippases-Structure, Function, and Enigmas. Frontiers in physiology 256 27458383
1981 Novel topologically knotted DNA from bacteriophage P4 capsids: studies with DNA topoisomerases. Nucleic acids research 234 6272191
2006 Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 197 16484372
1992 Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations. Arthritis and rheumatism 165 1418007
1993 Mechanisms of genome propagation and helper exploitation by satellite phage P4. Microbiological reviews 153 8246844
2012 Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII. Cell 150 22980978
2013 Systems biology and p4 medicine: past, present, and future. Rambam Maimonides medical journal 136 23908862
2019 Structure and autoregulation of a P4-ATPase lipid flippase. Nature 135 31243363
2014 Structure of an Rrp6-RNA exosome complex bound to poly(A) RNA. Nature 126 25043052
2012 Systems cancer medicine: towards realization of predictive, preventive, personalized and participatory (P4) medicine. Journal of internal medicine 125 22142401
2007 C1D and hMtr4p associate with the human exosome subunit PM/Scl-100 and are involved in pre-rRNA processing. Nucleic acids research 122 17412707
2012 Mammalian P4-ATPases and ABC transporters and their role in phospholipid transport. Biochimica et biophysica acta 119 23103747
2010 Execution of the meiotic noncoding RNA expression program and the onset of gametogenesis in yeast require the conserved exosome subunit Rrp6. Proceedings of the National Academy of Sciences of the United States of America 112 21149693
2013 P4 ATPases: flippases in health and disease. International journal of molecular sciences 110 23579954
2009 P4 ATPases - lipid flippases and their role in disease. Biochimica et biophysica acta 105 19254779
2007 Novel aspects of autoantibodies to the PM/Scl complex: clinical, genetic and diagnostic insights. Autoimmunity reviews 102 17643929
2014 P4-ATPases: lipid flippases in cell membranes. Pflugers Archiv : European journal of physiology 100 24077738
2014 The exosome-binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase. The EMBO journal 94 25319414
2009 Antibodies against PM/Scl-75 and PM/Scl-100 are independent markers for different subsets of systemic sclerosis patients. Arthritis research & therapy 93 19220911
2019 EXOSC10 is required for RPA assembly and controlled DNA end resection at DNA double-strand breaks. Nature communications 88 31086179
2008 Evidence for core exosome independent function of the nuclear exoribonuclease Rrp6p. Nucleic acids research 86 18940861
2009 TRAMP complex enhances RNA degradation by the nuclear exosome component Rrp6. The Journal of biological chemistry 85 19955569
2006 Structure of the nuclear exosome component Rrp6p reveals an interplay between the active site and the HRDC domain. Proceedings of the National Academy of Sciences of the United States of America 77 16882719
2007 The PMC2NT domain of the catalytic exosome subunit Rrp6p provides the interface for binding with its cofactor Rrp47p, a nucleic acid-binding protein. Nucleic acids research 75 17704127
1990 Interactions between satellite bacteriophage P4 and its helpers. Annual review of genetics 75 2088176
2014 Clinical and serologic correlates of anti-PM/Scl antibodies in systemic sclerosis: a multicenter study of 763 patients. Arthritis & rheumatology (Hoboken, N.J.) 73 24577935
2012 Rrp6p controls mRNA poly(A) tail length and its decoration with poly(A) binding proteins. Molecular cell 66 22683267
2001 NadN and e (P4) are essential for utilization of NAD and nicotinamide mononucleotide but not nicotinamide riboside in Haemophilus influenzae. Journal of bacteriology 66 11395461
2019 Rapid Depletion of DIS3, EXOSC10, or XRN2 Reveals the Immediate Impact of Exoribonucleolysis on Nuclear RNA Metabolism and Transcriptional Control. Cell reports 65 30840897
2011 Activities of human RRP6 and structure of the human RRP6 catalytic domain. RNA (New York, N.Y.) 64 21705430
2018 Yeast and human P4-ATPases transport glycosphingolipids using conserved structural motifs. The Journal of biological chemistry 63 30530492
1993 Phage P4 alpha protein is multifunctional with origin recognition, helicase and primase activities. The EMBO journal 62 8253092
2003 Contribution of domain structure to the RNA 3' end processing and degradation functions of the nuclear exosome subunit Rrp6p. RNA (New York, N.Y.) 59 12923258
1992 Cloning of a complementary DNA coding for the 100-kD antigenic protein of the PM-Scl autoantigen. The Journal of clinical investigation 59 1644924
2001 The plasmid status of satellite bacteriophage P4. Plasmid 56 11319927
1990 Identification of protein components reactive with anti-PM/Scl autoantibodies. Clinical and experimental immunology 56 2199097
2018 Phospholipid-flipping activity of P4-ATPase drives membrane curvature. The EMBO journal 55 29599178
1998 Structure and NTPase activity of the RNA-translocating protein (P4) of bacteriophage phi 6. Journal of molecular biology 55 9642042
2003 RNA packaging device of double-stranded RNA bacteriophages, possibly as simple as hexamer of P4 protein. The Journal of biological chemistry 50 12966097
2015 The exosome component Rrp6 is required for RNA polymerase II termination at specific targets of the Nrd1-Nab3 pathway. PLoS genetics 49 25680078
2010 Genome-wide analysis reveals distinct substrate specificities of Rrp6, Dis3, and core exosome subunits. RNA (New York, N.Y.) 48 20185544
2015 Anti-PM/Scl antibodies are found in Japanese patients with various systemic autoimmune conditions besides myositis and scleroderma. Arthritis research & therapy 47 25885224
1991 Parvovirus NS1 stimulates P4 expression by interaction with the terminal repeats and through DNA amplification. Journal of virology 47 1830114
2017 P4 medicine approach to obstructive sleep apnoea. Respirology (Carlton, Vic.) 46 28477347
2011 Rrp6, rrp47 and cofactors of the nuclear exosome. Advances in experimental medicine and biology 46 21713680
2007 Depletion of the yeast nuclear exosome subunit Rrp6 results in accumulation of polyadenylated RNAs in a discrete domain within the nucleolus. Molecular and cellular biology 46 17403903
2015 RRP6/EXOSC10 is required for the repair of DNA double-strand breaks by homologous recombination. Journal of cell science 44 25632158
2011 The incorporation of 5-fluorouracil into RNA affects the ribonucleolytic activity of the exosome subunit Rrp6. Molecular cancer research : MCR 44 21289297
1986 Organization and expression of the satellite bacteriophage P4 late gene cluster. Journal of molecular biology 44 3295254
2016 The Rrp6 C-terminal domain binds RNA and activates the nuclear RNA exosome. Nucleic acids research 43 27899565
2018 The H/ACA complex disrupts triplex in hTR precursor to permit processing by RRP6 and PARN. Nature communications 42 30575725
2010 P4 ATPases--the physiological relevance of lipid flipping transporters. FEBS letters 40 20450914
2009 Core exosome-independent roles for Rrp6 in cell cycle progression. Molecular biology of the cell 39 19225159
2020 EXOSC10 sculpts the transcriptome during the growth-to-maturation transition in mouse oocytes. Nucleic acids research 38 32313933
2010 Splice-site mutations cause Rrp6-mediated nuclear retention of the unspliced RNAs and transcriptional down-regulation of the splicing-defective genes. PloS one 38 20634951
2006 The subcellular localisation of trypanosome RRP6 and its association with the exosome. Molecular and biochemical parasitology 38 17118470
2016 Decoding P4-ATPase substrate interactions. Critical reviews in biochemistry and molecular biology 33 27696908
2015 Rrp6: Integrated roles in nuclear RNA metabolism and transcription termination. Wiley interdisciplinary reviews. RNA 33 26612606
1992 Bacteriophage P2 and P4 morphogenesis: protein processing and capsid size determination. Virology 33 1546453
2020 The transport mechanism of P4 ATPase lipid flippases. The Biochemical journal 32 33045059
2012 Fig mosaic emaravirus p4 protein is involved in cell-to-cell movement. The Journal of general virology 32 23152372
2021 Structural Basis of Substrate-Independent Phosphorylation in a P4-ATPase Lipid Flippase. Journal of molecular biology 30 34023399
2020 P4-ATPases: how an old dog learnt new tricks - structure and mechanism of lipid flippases. Current opinion in structural biology 30 32492637
2019 Hepatitis B virus X protein (HBx) enhances centrosomal P4.1-associated protein (CPAP) expression to promote hepatocarcinogenesis. Journal of biomedical science 30 31170980
2015 Nab3 facilitates the function of the TRAMP complex in RNA processing via recruitment of Rrp6 independent of Nrd1. PLoS genetics 30 25775092
2013 The exosome cofactor Rrp47 is critical for the stability and normal expression of its associated exoribonuclease Rrp6 in Saccharomyces cerevisiae. PloS one 30 24224060
2016 Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis. RNA (New York, N.Y.) 29 26857222
2013 Cotranscriptional recruitment of RNA exosome cofactors Rrp47p and Mpp6p and two distinct Trf-Air-Mtr4 polyadenylation (TRAMP) complexes assists the exonuclease Rrp6p in the targeting and degradation of an aberrant messenger ribonucleoprotein particle (mRNP) in yeast. The Journal of biological chemistry 29 24047896
2023 Activation and substrate specificity of the human P4-ATPase ATP8B1. Nature communications 28 37980352
2019 Identification and functional analyses of disease-associated P4-ATPase phospholipid flippase variants in red blood cells. The Journal of biological chemistry 27 30850395
2017 EXOSC10/Rrp6 is post-translationally regulated in male germ cells and controls the onset of spermatogenesis. Scientific reports 27 29118343
1996 Mapping of epitopes recognized by PM/Scl autoantibodies with gene-fragment phage display libraries. Journal of immunological methods 27 8946014
1995 Purification and characterization of the bacteriophage P4 delta protein. Journal of bacteriology 27 7601839
2014 Interactions of Rice tungro bacilliform pararetrovirus and its protein P4 with plant RNA-silencing machinery. Molecular plant-microbe interactions : MPMI 26 25122481
2020 Rrp6 Regulates Heterochromatic Gene Silencing via ncRNA RUF6 Decay in Malaria Parasites. mBio 25 32487761
2017 Myopenia and precision (P4) medicine. Journal of cachexia, sarcopenia and muscle 25 28944582
2017 The Luteovirus P4 Movement Protein Is a Suppressor of Systemic RNA Silencing. Viruses 25 28994713
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2013 Assembly of the yeast exoribonuclease Rrp6 with its associated cofactor Rrp47 occurs in the nucleus and is critical for the controlled expression of Rrp47. The Journal of biological chemistry 24 23580640
2006 Expression of phage P4 integrase is regulated negatively by both Int and Vis. The Journal of general virology 24 16847139
1995 Peptide presentation by bacteriophage P4. FEMS microbiology reviews 24 7669349
1994 Analysis of the specificity of anti-PM-Scl autoantibodies. Arthritis and rheumatism 23 7945469
2019 Phosphatidylserine flipping by the P4-ATPase ATP8A2 is electrogenic. Proceedings of the National Academy of Sciences of the United States of America 22 31371510
2012 Structure and size determination of bacteriophage P2 and P4 procapsids: function of size responsiveness mutations. Journal of structural biology 22 22508104
2023 The ubiquitin-specific protease USP36 SUMOylates EXOSC10 and promotes the nucleolar RNA exosome function in rRNA processing. Nucleic acids research 21 36912080
2021 Aminoglycerophospholipid flipping and P4-ATPases in Toxoplasma gondii. The Journal of biological chemistry 21 33485966
2019 An unusual and vital protein with guanylate cyclase and P4-ATPase domains in a pathogenic protist. Life science alliance 21 31235476
2010 Anti-PM/Scl-100 and anti-RNA-polymerase III antibodies in scleroderma. Clinica chimica acta; international journal of clinical chemistry 21 20346932
2010 Rrp6, Rrp47 and cofactors of the nuclear exosome. Advances in experimental medicine and biology 21 21618877
1998 Bacteriophage P2 and P4 morphogenesis: structure and function of the connector. Virology 20 9614863
1999 Effects of anti-PM-Scl 100 (Rrp6p exonuclease) antibodies on prenucleolar body dynamics at the end of mitosis. Experimental cell research 19 10471330
1985 Bacteriophage P4 DNA replication. Location of the P4 origin. Journal of molecular biology 19 2989532
2021 Dynamic membranes: the multiple roles of P4 and P5 ATPases. Plant physiology 18 33822217
2012 P4 down-regulates Jagged2 and Notch1 expression during primordial folliculogenesis. Frontiers in bioscience (Elite edition) 18 22652674
2012 Genetic interactions suggest multiple distinct roles of the arch and core helicase domains of Mtr4 in Rrp6 and exosome function. Nucleic acids research 18 23143101
2009 Interdependent nucleocytoplasmic trafficking and interactions of Dis3 with Rrp6, the core exosome and importin-alpha3. Traffic (Copenhagen, Denmark) 18 19220816
2007 Incorporation of scaffolding protein gpO in bacteriophages P2 and P4. Virology 18 17931675
2011 The PolyA tail length of yeast histone mRNAs varies during the cell cycle and is influenced by Sen1p and Rrp6p. Nucleic acids research 17 22123738

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