Affinage

EXOSC4

Exosome complex component RRP41 · UniProt Q9NPD3

Length
245 aa
Mass
26.4 kDa
Annotated
2026-04-28
70 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EXOSC4 (Rrp41) is a core structural subunit of the nine-subunit RNA exosome, a conserved 3′→5′ exoribonuclease complex that processes rRNA precursors, degrades mRNAs, and surveils non-coding transcripts. EXOSC4 contributes its RNase PH domain to the hexameric barrel through which RNA substrates are threaded to reach the catalytic Dis3/Rrp44 active site; evolutionarily conserved residues in EXOSC4 line this central channel and are required for both exonucleolytic and endonucleolytic activities of the complex (PMID:19879841, PMID:23404585). EXOSC4 is essential for exosome complex stability—its depletion causes co-depletion of other subunits—and it is one of the initiating subunits in the sequential assembly hierarchy of the mammalian exosome, with orphan EXOSC4 degraded by the ubiquitin–proteasome system (PMID:17545563, PMID:17174896). A pathogenic EXOSC4 missense variant (p.Leu187Pro) impairs exosome assembly, causes accumulation of 7S pre-rRNA, and compromises translational fidelity by allowing aberrant rRNA incorporation into polysomes (PMID:39009343).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1996 High

    Establishing that EXOSC4 (Rrp4p/Rrp41p orthologs) possesses 3′→5′ exoribonuclease activity and is required for 5.8S rRNA maturation answered the question of what nucleolytic activities process the 7S pre-rRNA intermediate.

    Evidence Temperature-sensitive yeast mutants, immunoprecipitated Rrp4p exonuclease assays, and affinity-purified exosome complex characterization

    PMID:8600032 PMID:9390555

    Open questions at the time
    • Whether EXOSC4/Rrp41 itself has intrinsic catalytic activity versus being a structural scaffold was not resolved
    • No structural information on the complex
  2. 1998 High

    Demonstrating that Rrp4p/Rrp41p depletion stabilizes mRNAs established the exosome as the machinery for 3′→5′ mRNA degradation, extending its role beyond rRNA processing.

    Evidence Genetic depletion with mRNA half-life measurements and epistasis with 5′→3′ decay mutants in yeast

    PMID:9482746

    Open questions at the time
    • Specific mRNA substrates were not identified
    • Whether cytoplasmic and nuclear degradation pathways differed was unknown
  3. 2000 High

    Identification of the human EXOSC4-containing exosome complex with 3′→5′ activity and nuclear/nucleolar enrichment established conservation of exosome function in mammals.

    Evidence Co-immunoprecipitation with patient autoantisera, size-exclusion chromatography, in vitro activity assays, subcellular fractionation, and yeast complementation

    PMID:11110791

    Open questions at the time
    • Stoichiometry and architecture of the human complex were unknown
    • Functional distinction between nuclear and cytoplasmic pools was not addressed
  4. 2002 Medium

    Mapping EXOSC4's RNase PH domain as an AU-rich element (ARE) RNA-binding module and showing it participates in a hexameric ring with at least two copies revealed its structural and substrate-recognition contributions.

    Evidence Recombinant domain binding assays, mammalian two-hybrid, and co-immunoprecipitation

    PMID:12419256 PMID:16912217

    Open questions at the time
    • Whether ARE binding by EXOSC4 contributes to substrate selection in vivo was untested
    • Stoichiometry of two copies per complex was not confirmed structurally
  5. 2003 High

    Showing that EXOSC4 knockdown stabilizes nonsense-containing mRNAs and that NMD factors co-purify with EXOSC4 linked the exosome to nonsense-mediated mRNA decay.

    Evidence siRNA knockdown with mRNA stability assays and co-immunoprecipitation of Upf1/Upf2/Upf3X with Rrp41

    PMID:14527413

    Open questions at the time
    • Whether the exosome is recruited directly by NMD factors or acts downstream was unclear
    • Relative contribution of 3′→5′ versus 5′→3′ decay in NMD was not resolved
  6. 2006 High

    Determination of the 3.35 Å crystal structure of the nine-subunit human exosome revealed EXOSC4 as part of the barrel architecture with phosphorolytic activity residing in the Rrp41/Rrp45 heterodimer, resolving the long-standing question of complex organization.

    Evidence X-ray crystallography and in vitro reconstitution with biochemical activity assays

    PMID:17174896

    Open questions at the time
    • Whether the phosphorolytic activity of the barrel is physiologically relevant in the context of the Dis3-containing holoenzyme was debated
    • No RNA-bound structure
  7. 2007 Medium

    Knockdown experiments showing that EXOSC4 depletion co-depletes other subunits identified it as a structural keystone required for exosome complex stability, distinguishing it from peripheral components.

    Evidence siRNA knockdown with glycerol gradient sedimentation and Western blot of subunit levels

    PMID:17545563

    Open questions at the time
    • Mechanism of co-depletion (degradation pathway of orphan subunits) was unknown
    • Whether EXOSC4 depletion affects nuclear and cytoplasmic complexes equally was unclear
  8. 2009 High

    Crystal structures of RNA-bound exosome showed that substrates thread through the central channel lined by EXOSC4/Rrp41 residues to reach Dis3/Rrp44, establishing the channeling mechanism as essential for processive degradation.

    Evidence 3.0 Å X-ray crystallography with RNA substrate and biochemical assays using channel-blocking mutants

    PMID:19879841

    Open questions at the time
    • In vivo validation of the channeling mechanism was lacking
    • Whether all substrates use the channel or some bypass it was unknown
  9. 2012 High

    Transcriptome-wide in vivo crosslinking demonstrated direct RNA contacts by Rrp41 and identified diverse substrate classes (CUTs, SUTs, snoRNAs, pre-tRNAs, pre-mRNAs), answering the question of what the exosome channel engages in living cells.

    Evidence CRAC (UV crosslinking and cDNA analysis) of tagged Rrp41 in yeast

    PMID:23000172

    Open questions at the time
    • Substrate selectivity determinants were not defined
    • Human in vivo crosslinking data were not available
  10. 2013 High

    Channel-blocking Rrp41 mutants caused substrate accumulation and synthetic lethality with Rrp6 deletion, proving in vivo that the central channel controls both exonucleolytic and endonucleolytic Dis3 activities.

    Evidence Channel-blocking mutagenesis in Chaetomium thermophilum exosome, in vitro reconstitution, yeast genetic epistasis

    PMID:23404585

    Open questions at the time
    • Quantitative contribution of channel vs. direct-access routes for different substrate classes remained unresolved
  11. 2017 High

    Transcriptome-wide analysis of Rrp41 channel mutants showed that cytoplasmic mRNAs preferentially require channel threading while nuclear substrates can use alternative direct-access routes, resolving the compartment-specific routing question.

    Evidence CRAC with Rrp41 mutants, genome-wide comparison of threading vs. direct-access pathways in yeast

    PMID:28355211

    Open questions at the time
    • Whether this dual routing applies in human cells was untested
    • Molecular determinants selecting substrates for each route were not identified
  12. 2024 High

    A pathogenic EXOSC4 missense variant (L187P) was shown to impair protein stability, exosome assembly, 7S pre-rRNA processing, and translation, directly connecting EXOSC4 structural integrity to human disease.

    Evidence Exome sequencing, yeast modeling, co-immunoprecipitation, Northern blot for rRNA intermediates, polysome profiling

    PMID:39009343

    Open questions at the time
    • Full clinical spectrum of EXOSC4 mutations not delineated
    • Whether translation defects are secondary to aberrant rRNA or reflect an additional function is unclear
    • Structural basis of L187P destabilization not modeled
  13. 2025 Medium

    Systematic CRISPR-based dissection and humanized yeast complementation established EXOSC4 as an initiating subunit in a hierarchical exosome assembly pathway, with orphan EXOSC4 cleared by ubiquitin-proteasome-mediated degradation, and confirmed that disease variants cause functional defects in this pathway.

    Evidence Inducible dual-guide CRISPR knockout in mouse ES cells with co-IP/MS; humanized yeast complementation with disease variants

    PMID:39982806

    Open questions at the time
    • Assembly pathway data from preprint awaits peer review
    • E3 ligase responsible for orphan EXOSC4 degradation is unidentified
    • Whether assembly hierarchy is tissue-specific is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the E3 ubiquitin ligase targeting orphan EXOSC4, the structural basis of disease-associated variants on channel architecture, and whether EXOSC4-mediated chromatin recruitment via modified histones represents a physiological targeting mechanism.
  • No E3 ligase for orphan EXOSC4 identified
  • No high-resolution structure of disease variant exosomes
  • Chromatin recruitment via H3K9me3 reported only in a single preprint

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 4 GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005730 nucleolus 1
Pathway
R-HSA-8953854 Metabolism of RNA 8 R-HSA-168256 Immune System 1 R-HSA-392499 Metabolism of proteins 1
Partners
DIS3EXOSC2EXOSC5EXOSC7EXOSC9UPF1ZC3HAV1
Complex memberships
RNA exosome core (Exo-9)RNA exosome holoenzyme (Exo-10/11)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 EXOSC4 (yeast Rrp4p) is a component of the exosome, a multi-subunit 3'→5' exoribonuclease complex; recombinant Rrp4p exhibits distributive 3'→5' exoribonuclease activity in vitro requiring a 3'-terminal hydroxyl and releasing nucleoside 5' monophosphates. All exosome components including Rrp4p are required for 3' processing of 5.8S rRNA. Affinity purification/MS identification of complex, in vitro exoribonuclease assay with recombinant protein, genetic depletion with rRNA processing phenotype Cell High 9390555
1996 Rrp4p (yeast ortholog of EXOSC4) is required for 3'→5' exonucleolytic processing of the 7S pre-rRNA precursor to mature 5.8S rRNA; immunoprecipitated Rrp4p exhibits 3'→5' exoribonuclease activity in vitro. Temperature-sensitive mutant analysis, complementation cloning, immunoprecipitation followed by in vitro exoribonuclease assay Genes & development High 8600032
1998 Rrp4p (yeast EXOSC4 ortholog) and Ski6p/Rrp41p are required for the 3'→5' degradation pathway of mRNA in yeast, establishing the exosome as the nucleolytic activity that degrades mRNA bodies in the 3'→5' direction. Genetic depletion/mutation of RRP4 and SKI6/RRP41 with mRNA half-life measurement; epistasis with 5'→3' decay mutants The EMBO journal High 9482746
2000 Human Rrp41p (EXOSC4) physically associates with other human exosome components including hRrp4p, hRrp40p, hRrp46p, and PM/Scl-100 in a large complex; the immunoprecipitated human exosome complex exhibits 3'→5' exoribonuclease activity in vitro. hRrp41p is enriched in the nucleus and nucleolus but also detected in the cytoplasm. Co-immunoprecipitation with patient autoantisera, size exclusion chromatography, in vitro exoribonuclease assay, subcellular fractionation/Western blot, complementation of yeast rrp41 null mutant The Journal of biological chemistry High 11110791
2002 hRrp41p (EXOSC4) RNase PH domain specifically binds AU-rich element (ARE)-containing RNAs in a sequence-specific manner, with similar affinities to other exosomal RNase PH domains; poly(U) efficiently competes this interaction. Deletion mutagenesis, RNA binding assays with recombinant RNase PH domain fragments, competition assays RNA (New York, N.Y.) Medium 16912217
2002 Human EXOSC4 (hRrp41p) interacts with other RNase PH-like exosome subunits to form a hexameric ring structure; mammalian two-hybrid and co-immunoprecipitation analyses show at least two copies of hRrp41p associated with a single exosome complex. Mammalian two-hybrid protein-protein interaction assay, co-immunoprecipitation Journal of molecular biology Medium 12419256
2003 PM/Scl-75 (EXOSC9) association with the human exosome is mediated in part through protein-protein interactions with hRrp46p and hRrp41p (EXOSC4), as confirmed by mammalian two-hybrid; nuclear localization signal of PM/Scl-75 is required for nucleolar but not exosome association. Mammalian two-hybrid, deletion mutagenesis, co-immunoprecipitation The Journal of biological chemistry Medium 12788944
2003 Downregulation of exosomal component Rrp41 (EXOSC4) significantly increases the abundance and slows the decay rate of nonsense-containing mRNAs in mammalian cells, establishing EXOSC4-containing exosome as a component of the nonsense-mediated mRNA decay (NMD) pathway. NMD factors Upf1, Upf2, and Upf3X co-immunopurify with Rrp41. siRNA knockdown with mRNA stability assay, co-immunoprecipitation Molecular cell High 14527413
2006 The 9-subunit human exosome containing EXOSC4 (hRrp41) was reconstituted in vitro; the human Rrp41/Rrp45 heterodimer exhibits processive phosphorolytic activity and the reconstituted 9-subunit human exosome also shows processive phosphorolytic activity. The X-ray crystal structure of the 286 kDa nine-subunit human exosome was determined at 3.35 Å, revealing its barrel architecture. Recombinant protein reconstitution, biochemical activity assays, X-ray crystallography Cell High 17174896
2006 Zinc-finger antiviral protein (ZAP) directly interacts with human exosome component hRrp46p and recruits the RNA processing exosome (including hRrp41p/EXOSC4) to degrade viral target mRNAs; depletion of hRrp41p by siRNA significantly reduces ZAP's mRNA destabilizing activity. Sucrose/glycerol velocity gradient sedimentation, immunoprecipitation, in vitro pull-down assay, siRNA knockdown with mRNA stability assay Proceedings of the National Academy of Sciences of the United States of America Medium 17185417
2007 EXOSC4 (hRrp41p) knockdown but not PM/Scl-100 or PM/Scl-75 knockdown leads to co-depletion of other exosome subunits, identifying EXOSC4 as a structural subunit required for exosome complex stability. Nuclear exosome is present in much larger complexes (60–80S) than cytoplasmic exosomes (~10S). siRNA knockdown, glycerol gradient sedimentation, Western blot analysis of subunit co-depletion, mRNA reporter stability assays RNA (New York, N.Y.) Medium 17545563
2007 The mRNA encoding Rrp41 (EXOSC4) is a specific substrate of human Dcp2 decapping enzyme; a 60-nucleotide element at the 5' end of Rrp41 mRNA confers more efficient decapping both in vitro and in cells, and reduction of hDcp2 selectively stabilizes Rrp41 mRNA. In vitro decapping assay, RNA binding assay, transfection reporter assay, siRNA knockdown of hDcp2 with mRNA stability readout Molecular and cellular biology Medium 18039849
2009 RNAs thread through the central channel of the exosome core (involving Rrp41/EXOSC4 subunit) to reach the Rrp44 exoribonuclease active site; this channeling mechanism involves evolutionarily conserved residues in Rrp41, allows processive unwinding and degradation of RNA duplexes without helicase. X-ray crystallography (3.0 Å), biochemical RNA degradation assays with channel mutants Cell High 19879841
2012 In vivo UV crosslinking (CRAC) analysis showed that core exosome subunit Rrp41 (EXOSC4 ortholog) directly contacts RNA substrates; transcriptome-wide identification of exosome targets including CUTs, SUTs, snoRNAs, pre-tRNAs, and unspliced pre-mRNAs as Rrp41-associated substrates. In vivo UV crosslinking and cDNA analysis (CRAC) of tagged Rrp41 Molecular cell High 23000172
2013 An Rrp41 (EXOSC4 ortholog) mutant with a partially blocked central channel causes thermosensitivity, accumulation of nuclear and cytoplasmic exosome substrates, and synthetic lethality with Rrp6 deletion, demonstrating that the central channel controls both exonucleolytic and endonucleolytic Dis3/Rrp44 activities in vivo. Channel-blocking mutagenesis, in vitro reconstitution with Chaetomium thermophilum exosomes, genetic epistasis (synthetic lethality), RNA substrate accumulation assays Nucleic acids research High 23404585
2014 Knockdown of RRP41 (EXOSC4 ortholog) stabilizes U12-type intron-containing pre-mRNAs and globally upregulates U12-type intron retention in human cells, establishing EXOSC4-containing exosome as a factor in nuclear decay of transcripts with retained minor spliceosome introns. siRNA knockdown of RRP41, SOLiD RNA sequencing, decay kinetics analysis Nucleic acids research Medium 24848017
2017 Transcriptome-wide CRAC analysis in yeast established that Rrp41 (EXOSC4 ortholog) mutations that impede RNA access to the central channel block substrate passage to Rrp44 specifically for cytoplasmic mRNAs, while nuclear mRNAs can use alternative direct-access routes; many exosome substrates show clear preferences for specific pathways to Rrp44. CRAC (UV crosslinking and cDNA analysis) with Rrp41 mutants, transcriptome-wide analysis, comparison of threading vs. direct-access routes PLoS genetics High 28355211
2020 EXOSC2/EXOSC4 depletion attenuates P-body formation and stress resistance in cancer cells, with EXOSC4 knockdown causing decreased EXOSC9 protein levels, linking EXOSC4 to exosome complex stability and stress-adaptive mRNP granule formation. siRNA knockdown, P-body counting by microscopy, Western blot analysis of protein levels Scientific reports Medium 32518284
2022 EXOSC4 knockdown in pancreatic cancer cells reduces cell viability; EXOSC4 represses BIK expression and destabilizes SESN2 mRNA by promoting its degradation, establishing specific mRNA substrates regulated by EXOSC4. siRNA knockdown, mRNA stability assay, Western blot, cell viability assay, rescue experiments with BIK and SESN2 knockdown International journal of molecular sciences Medium 35008922
2024 A pathogenic missense variant in EXOSC4 (p.Leu187Pro) reduces steady-state protein levels, decreases co-purification of EXOSC4-L187P with other RNA exosome subunits, causes accumulation of 7S pre-rRNA (an exosome target), and leads to incorporation of 7S pre-rRNA into polysomes with decreased translational activity, linking EXOSC4 structural integrity to exosome assembly, rRNA processing, and translation. Exome sequencing, Sanger sequencing, yeast modeling (Rrp41-L187P), growth assays, co-purification (Western blot of co-immunoprecipitation), RNA northern blot, polysome profiling The Journal of biological chemistry High 39009343
2024 EXOSC4 interacts with histone H3 co-modified with K9me3 and acetylations; EXOSC4 depletion leads to downregulation of RNA surveillance machinery and increased expression of non-coding transcripts including antisense RNAs, establishing EXOSC4 as a chromatin-recruited factor for surveillance of non-coding transcription. Multi-dimensional mass spectrometry, histone modification-based pulldown, EXOSC4 depletion with transcriptome analysis bioRxivpreprint Low bio_10.1101_2024.08.05.606680
2025 EXOSC4 is among the initiating subunits (along with EXOSC2 and EXOSC7) in a sequential assembly pathway of the mammalian RNA exosome; EXOSC4 facilitates incorporation of barrel and cap subunits in a defined hierarchy. Orphan EXOSC4 (not incorporated into the complex) is selectively degraded via the ubiquitin-proteasome system. Inducible dual-guide CRISPR/Cas9 knockout system in mouse embryonic stem cells, co-immunoprecipitation/MS to track subunit incorporation, proteasome inhibitor experiments bioRxivpreprint Medium bio_10.1101_2025.03.14.643291
2025 In a humanized yeast model, human EXOSC4 can replace the orthologous yeast Rrp41 and support near-normal growth; disease-associated variants of EXOSC4 show functional defects in this humanized yeast exosome, with a subset causing reduced protein levels and others showing activity defects at normal expression levels. Humanized yeast complementation (replacement of yeast subunit with human ortholog), growth assays, Western blot for protein levels G3 (Bethesda, Md.) Medium 39982806

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 The exosome: a conserved eukaryotic RNA processing complex containing multiple 3'-->5' exoribonucleases. Cell 807 9390555
1998 The 3' to 5' degradation of yeast mRNAs is a general mechanism for mRNA turnover that requires the SKI2 DEVH box protein and 3' to 5' exonucleases of the exosome complex. The EMBO journal 545 9482746
2006 Reconstitution, activities, and structure of the eukaryotic RNA exosome. Cell 449 17174896
2006 A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nature structural & molecular biology 353 17173052
2003 Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities. Molecular cell 306 14527413
1998 Dob1p (Mtr4p) is a putative ATP-dependent RNA helicase required for the 3' end formation of 5.8S rRNA in Saccharomyces cerevisiae. The EMBO journal 278 9463390
2006 The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA. Proceedings of the National Academy of Sciences of the United States of America 233 17185417
2009 The yeast exosome functions as a macromolecular cage to channel RNA substrates for degradation. Cell 207 19879841
1996 The 3' end of yeast 5.8S rRNA is generated by an exonuclease processing mechanism. Genes & development 187 8600032
2005 The archaeal exosome core is a hexameric ring structure with three catalytic subunits. Nature structural & molecular biology 185 15951817
2012 Transcriptome-wide analysis of exosome targets. Molecular cell 163 23000172
2002 Processing of 3'-extended read-through transcripts by the exosome can generate functional mRNAs. Molecular cell 139 12086625
2003 An exosome-like complex in Sulfolobus solfataricus. EMBO reports 118 12947419
2000 Poly(A) tail-dependent exonuclease AtRrp41p from Arabidopsis thaliana rescues 5.8 S rRNA processing and mRNA decay defects of the yeast ski6 mutant and is found in an exosome-sized complex in plant and yeast cells. The Journal of biological chemistry 112 10930416
2005 Structural basis of 3' end RNA recognition and exoribonucleolytic cleavage by an exosome RNase PH core. Molecular cell 102 16285928
2000 Three novel components of the human exosome. The Journal of biological chemistry 101 11110791
2007 RNA channelling by the archaeal exosome. EMBO reports 99 17380186
2007 Architecture of the yeast Rrp44 exosome complex suggests routes of RNA recruitment for 3' end processing. Proceedings of the National Academy of Sciences of the United States of America 92 17942686
2014 Genome-wide study of hypomethylated and induced genes in patients with liver cancer unravels novel anticancer targets. Clinical cancer research : an official journal of the American Association for Cancer Research 91 24763612
2005 A nuclear surveillance pathway for mRNAs with defective polyadenylation. Molecular and cellular biology 85 16260613
2002 Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. Journal of molecular biology 82 12419256
2007 Human cell growth requires a functional cytoplasmic exosome, which is involved in various mRNA decay pathways. RNA (New York, N.Y.) 73 17545563
2001 Autoantibodies directed to novel components of the PM/Scl complex, the human exosome. Arthritis research 72 11879549
2006 Microarray detection of novel nuclear RNA substrates for the exosome. Yeast (Chichester, England) 62 16652390
2007 Transcript-specific decapping and regulated stability by the human Dcp2 decapping protein. Molecular and cellular biology 54 18039849
2013 The RNA exosome complex central channel controls both exonuclease and endonuclease Dis3 activities in vivo and in vitro. Nucleic acids research 50 23404585
2008 Insights into the mechanism of progressive RNA degradation by the archaeal exosome. The Journal of biological chemistry 50 18353775
2006 Characterization of native and reconstituted exosome complexes from the hyperthermophilic archaeon Sulfolobus solfataricus. Molecular microbiology 46 17078816
2018 Diversity of copy number variation in the worldwide goat population. Heredity 44 30401973
2024 Genomic hallmarks and therapeutic targets of ribosome biogenesis in cancer. Briefings in bioinformatics 39 38343327
2017 Transcriptome-wide analysis of alternative routes for RNA substrates into the exosome complex. PLoS genetics 36 28355211
2017 RNA degradation by the plant RNA exosome involves both phosphorolytic and hydrolytic activities. Nature communications 33 29255150
2015 Genome-wide screen of DNA methylation identifies novel markers in childhood obesity. Gene 32 25871514
2006 Sequence-specific RNA binding mediated by the RNase PH domain of components of the exosome. RNA (New York, N.Y.) 32 16912217
2014 Structure and function of the archaeal exosome. Wiley interdisciplinary reviews. RNA 30 24789718
2020 EXOSC9 depletion attenuates P-body formation, stress resistance, and tumorigenicity of cancer cells. Scientific reports 29 32518284
2014 Global analysis of the nuclear processing of transcripts with unspliced U12-type introns by the exosome. Nucleic acids research 29 24848017
2022 The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families. Scientific reports 27 36344539
2012 RRP41L, a putative core subunit of the exosome, plays an important role in seed germination and early seedling growth in Arabidopsis. Plant physiology 25 23132787
2009 Mutational analysis of a Dcp2-binding element reveals general enhancement of decapping by 5'-end stem-loop structures. Nucleic acids research 24 19233875
2003 The association of the human PM/Scl-75 autoantigen with the exosome is dependent on a newly identified N terminus. The Journal of biological chemistry 24 12788944
2016 TMV induces RNA decay pathways to modulate gene silencing and disease symptoms. The Plant journal : for cell and molecular biology 22 27599263
2012 Heterogeneous complexes of the RNA exosome in Sulfolobus solfataricus. Biochimie 22 22503705
2010 The evolutionarily conserved subunits Rrp4 and Csl4 confer different substrate specificities to the archaeal exosome. FEBS letters 21 20488184
2018 EXOSC4 functions as a potential oncogene in development and progression of colorectal cancer. Molecular carcinogenesis 18 30155936
2010 The archaeal exosome localizes to the membrane. FEBS letters 15 20488181
2019 miR‑148 family members are putative biomarkers for sepsis. Molecular medicine reports 14 31059023
2022 RNA Exosome Component EXOSC4 Amplified in Multiple Cancer Types Is Required for the Cancer Cell Survival. International journal of molecular sciences 13 35008922
2016 The oligomeric architecture of the archaeal exosome is important for processive and efficient RNA degradation. Nucleic acids research 13 26837575
2021 Nrd1p identifies aberrant and natural exosomal target messages during the nuclear mRNA surveillance in Saccharomyces cerevisiae. Nucleic acids research 11 34664673
2021 Exosome Component 4 Promotes Epithelial Ovarian Cancer Cell Proliferation, Migration, and Invasion via the Wnt Pathway. Frontiers in oncology 10 34956910
2020 Nucleolar localization of the yeast RNA exosome subunit Rrp44 hints at early pre-rRNA processing as its main function. The Journal of biological chemistry 10 32554806
2018 Altered expression of WFS1 and NOTCH2 genes associated with diabetic nephropathy in T2DM patients. Diabetes research and clinical practice 10 29626590
2024 A biallelic variant of the RNA exosome gene, EXOSC4, associated with neurodevelopmental defects impairs RNA exosome function and translation. The Journal of biological chemistry 7 39009343
2020 STX2 drives colorectal cancer proliferation via upregulation of EXOSC4. Life sciences 7 33075373
2011 The archaeal exosome. Advances in experimental medicine and biology 7 21713675
2013 Experimental analysis of co-evolution within protein complexes: the yeast exosome as a model. Proteins 6 23852635
2012 Plant Exosomes and Cofactors. The Enzymes 6 27166439
2024 RUNX3 exerts tumor-suppressive role through inhibiting EXOSC4 expression. Functional & integrative genomics 5 38913281
2010 The archaeal exosome. Advances in experimental medicine and biology 5 21618872
2023 In vivo characterization of the critical interaction between the RNA exosome and the essential RNA helicase Mtr4 in Saccharomyces cerevisiae. G3 (Bethesda, Md.) 4 36861343
2021 m6A Regulator Expression Segregates Meningiomas Into Biologically Distinct Subtypes. Frontiers in oncology 4 35004283
2022 The Revelation of Continuously Organized, Co-Overexpressed Protein-Coding Genes with Roles in Cellular Communications in Breast Cancer. Cells 3 36497066
2025 Uncovering the genetic basis of milk production traits in Mexican Holstein cattle based on individual markers and genomic windows. PloS one 2 39899530
2025 Identification EXOSC4 as a novel autoantigen of interstitial lung disease in rheumatoid arthritis. Journal of translational medicine 2 40640919
2026 Ribosomal Protein RPL29 Promotes Hepatocellular Carcinoma Progression Through Regulation the Expression of Exosome Component 4. Biological procedures online 0 41484694
2025 Humanized Saccharomyces cerevisiae provides a facile and effective tool to identify damaging human variants that cause exosomopathies. G3 (Bethesda, Md.) 0 39982806
2023 A Biallelic Variant of the RNA Exosome Gene EXOSC4 Causes Translational Defects Associated with a Neurodevelopmental Disorder. medRxiv : the preprint server for health sciences 0 37961665
2023 [Expression and Clinical Significance of Exosome Component 4 in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma]. Zhongguo shi yan xue ye xue za zhi 0 38071046
2020 Enzymatic Analysis of Reconstituted Archaeal Exosomes. Methods in molecular biology (Clifton, N.J.) 0 31768972