Affinage

SRRT

Serrate RNA effector molecule homolog · UniProt Q9BXP5

Length
876 aa
Mass
100.7 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SRRT (ARS2) is an essential, predominantly nuclear metazoan protein that operates at the nexus of co-transcriptional RNA fate determination, acting as a hub that associates with the nuclear cap-binding complex (CBC) on capped Pol II transcripts and channels them toward processing, export, termination, or decay (PMID:24270878, PMID:28973446, PMID:18086880). Through mutually exclusive interactions it partitions transcripts between pathways: CBC-ARS2-PHAX promotes snRNA 3'-end processing and cap-proximal polyadenylation, whereas a CBC-NELF-E complex (incompatible with PHAX) acts at an earlier transcriptional phase, and a CBC-ARS2-NCBP3 complex directs mRNA export (PMID:24270878, PMID:29703953, PMID:29101316). Distinct ARS2 surfaces engage FLASH for replication-dependent histone mRNA 3'-end formation and the restrictor factor ZC3H4, which ARS2 recruits to chromatin via an acidic SLiM to drive CPA- and Integrator-independent Pol II termination coupled to nuclear-exosome (NEXT/PAXT) degradation of non-coding and pervasive transcripts; its zinc-finger domain is required both for these RNA-decay functions and for interaction with the RNA helicase MTR4 (PMID:29703953, PMID:28973446, PMID:37329882, PMID:37329883, PMID:32463452). Domain dissection maps the DUF3546 and ZnF domains to RNA and FLASH binding, the Mid domain to DROSHA interaction, the unstructured C-terminus to CBP20/CBC binding, and the metazoan-specific RRM to cell-cycle progression and FLASH binding (PMID:29703953, PMID:26303529). Independently of its RNA-processing roles, ARS2 promotes miRNA biogenesis by stabilizing pri-miRNAs and facilitating Microprocessor/DROSHA activity (PMID:19632183, PMID:19632182, PMID:26303529), and it acts as a sequence-specific DNA-binding transcription factor at neural stem cell enhancers, directly activating Sox2 to maintain NSC identity in a manner retained in Drosha/Dicer-null cells (PMID:22198669, PMID:31969356). ARS2 is essential for early mammalian development and for neural stem cell proliferation and neuronal differentiation (PMID:18086880, PMID:31969356).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2009 High

    Established ARS2 as a required factor for small-RNA silencing pathways, the first mechanistic role assigned to the protein, by linking it physically and functionally to both the siRNA machinery and the Microprocessor.

    Evidence Co-IP with Dcr-2 and Microprocessor, in vitro activity assays, and RNAi knockdown with siRNA/miRNA/antiviral readouts in Drosophila and mammalian cells

    PMID:19632182 PMID:19632183

    Open questions at the time
    • Did not resolve whether pri-miRNA stabilization is separable from CBC association
    • Structural basis of Microprocessor engagement not defined
  2. 2007 Medium

    Defined ARS2 as a nuclear protein essential for early mammalian development, framing it as a core RNA-metabolism factor before its molecular activities were known.

    Evidence Conditional knockout mice, immunofluorescence localization, blastocyst culture and TUNEL apoptosis assay

    PMID:18086880

    Open questions at the time
    • Lethality phenotype not assigned to a specific molecular pathway
    • No domain or interactor mapping
  3. 2011 High

    Revealed an RNA-independent function: ARS2 acts as a direct transcription factor binding the Sox2 NSC enhancer to sustain neural stem cell identity, dissociating part of its biology from miRNA processing.

    Evidence ChIP, EMSA, conditional KO mice, neurosphere assays and Sox2 rescue, with function retained in Drosha/Dicer1-null NSCs

    PMID:22198669

    Open questions at the time
    • DNA-binding domain within ARS2 not mapped at the time
    • Generality of direct enhancer binding beyond Sox2 unaddressed
  4. 2012 High

    Connected ARS2 to replication-dependent histone mRNA 3'-end formation, showing it biases transcripts toward correct cleavage over polyadenylation in a 7SK-dependent manner.

    Evidence RIP, qRT-PCR, siRNA knockdown and 3'-end processing assays with 7SK epistasis

    PMID:22244333

    Open questions at the time
    • Direct molecular link between ARS2 and the histone processing machinery not yet structural
    • Role of 7SK association mechanistically unresolved
  5. 2013 High

    Reconstituted the CBC-ARS2-PHAX (CBCAP) complex, establishing ARS2 as a CBC adaptor that stimulates PHAX recruitment and snRNA 3'-end processing and links to Pol II via CLP1/PCF11.

    Evidence Recombinant ternary-complex reconstitution, Co-IP, in vivo 3'-end processing assays and ChIP

    PMID:24270878

    Open questions at the time
    • How transcript identity selects PHAX versus other partners not defined here
    • Stoichiometry on chromatin unresolved
  6. 2015 Medium

    Produced a domain map of ARS2 assigning specific surfaces to RNA, FLASH, DROSHA and CBP20 binding and to cell-cycle progression, rationalizing how one hub serves multiple pathways.

    Evidence Site-directed mutagenesis, Co-IP, RIP and flow-cytometry cell-cycle analysis

    PMID:26303529

    Open questions at the time
    • Interactions tested largely pairwise without competition mapping
    • Functional consequences of individual mutants in vivo limited
  7. 2017 High

    Defined ARS2 as a genome-wide suppressor of pervasive transcription coupled to termination and exosome-mediated turnover, and identified ZC3H18 as a physical partner linking it to RNA decay.

    Evidence GRO-seq, RNA-seq, ChIP-seq with ARS2, ZC3H18 and exosome depletions for epistasis

    PMID:28973446

    Open questions at the time
    • Mechanism distinguishing termination from decay roles not fully separated
    • Direct chromatin-recruitment mechanism not defined
  8. 2017 High

    Showed that NELF-E and ARS2 bind CBC through identical C-terminal motifs, defining mutually exclusive CBC-NELF-E and CBC-ARS2-PHAX complexes that act in distinct transcriptional phases.

    Evidence X-ray crystallography of CBC-NELF-E, ITC binding measurements and mutagenesis

    PMID:29101316

    Open questions at the time
    • Temporal switch between complexes not directly observed in cells
    • Cap-enhancement effect on partner choice not quantified genome-wide
  9. 2018 High

    Resolved the human ARS2 structure, revealing a metazoan-specific RRM absent in plant SERRATE and mapping overlapping FLASH/NCBP3 sites that explain mutually exclusive CBC-ARS2-NCBP3 versus CBC-ARS2-PHAX complexes.

    Evidence X-ray crystallography, biochemical and biophysical binding assays, MS interactome and mutagenesis

    PMID:29703953

    Open questions at the time
    • How RRM-mediated ssRNA binding integrates with partner selection unresolved
    • In vivo dynamics of complex switching not captured
  10. 2018 Medium

    Extended ARS2's miRNA-processing role to disease, showing CBC-dependent ARS2 function controls a miRNA that regulates p27 and cell-cycle progression in leukemia cells.

    Evidence Co-IP, shRNA knockdown, miRNA qRT-PCR, cell-cycle flow cytometry and xenograft

    PMID:30518811

    Open questions at the time
    • miR-6734-3p/p27 axis specificity to AML unclear
    • Direct ARS2-Microprocessor mechanism not re-examined
  11. 2020 Medium

    Localized ARS2's RNA-decay activity to its zinc-finger domain and linked it to the PAXT helicase MTR4, showing CBC binding is dispensable when ARS2 is tethered directly to RNA.

    Evidence Tethering reporter decay assay and Co-IP domain mapping with ARS2 mutants

    PMID:32463452

    Open questions at the time
    • Direct ZnF-MTR4 contact versus bridged interaction not distinguished
    • How decay versus processing is selected unresolved
  12. 2020 Medium

    Showed ARS2 governs NEAT1 isoform choice and paraspeckle abundance by enabling NEAT1-CFIm association, extending its fate-determination role to a structural lncRNA.

    Evidence siRNA knockdown, NEAT1-CFIm RIP, paraspeckle imaging and qRT-PCR

    PMID:31818879

    Open questions at the time
    • Direct ARS2-CFIm contact not demonstrated
    • Whether effect is co-transcriptional unresolved
  13. 2020 Medium

    Demonstrated in vivo that ARS2 occupies NSC enhancers genome-wide and colocalizes with SOX2, generalizing its chromatin transcription-factor role and tying it to neurogenesis across embryonic and adult stages.

    Evidence Embryonic and adult conditional KO mice, ChIP-seq, behavioral assays and immunofluorescence

    PMID:31969356

    Open questions at the time
    • Direct DNA-recognition determinant within ARS2 still unmapped
    • Mechanistic separation from RNA-processing roles in vivo incomplete
  14. 2020 Medium

    Showed conservation of ARS2-associated RNA-silencing in fission yeast Pir2 and identified splicing-factor association as a recurring ARS2 interaction also present in human cells.

    Evidence Co-IP in S. pombe, RNA-seq, ChIP-seq and genetic epistasis with splicing-factor mutants

    PMID:32415063

    Open questions at the time
    • Whether splicing-factor recruitment is direct unresolved in human cells
    • Cryptic-intron targeting mechanism not fully defined
  15. 2020 Medium

    Connected ARS2's transcription-factor activity to cancer biology, showing direct activation of MGLL drives PGE2 production and immunosuppressive signaling in glioblastoma stem cells.

    Evidence ChIP, luciferase reporter, knockdown and xenograft model

    PMID:32532977

    Open questions at the time
    • DNA-binding determinant for MGLL promoter not mapped
    • Generality of direct gene activation beyond MGLL/Sox2 unclear
  16. 2022 Medium

    Revealed an ortholog-specific adaptor mechanism in C. elegans where SNA-3 bridges the SL1 snRNP to CBC-ARS2, implicating ARS2 in trans-splicing.

    Evidence Reciprocal IP, RIP-seq, mass spectrometry, yeast two-hybrid and localization microscopy

    PMID:35736244

    Open questions at the time
    • SNA-3 has no mammalian equivalent identified here
    • Relevance to vertebrate splicing unclear
  17. 2023 High

    Defined the molecular mechanism of ARS2-driven early termination: a basic ARS2 domain binds an acidic SLiM in ZC3H4 to recruit restrictor to chromatin, eliciting CPA/Integrator-independent termination and NEXT-coupled decay of ncRNAs, gated by PNUTS and shielded by U1 snRNA.

    Evidence Reciprocal Co-IP, domain mutagenesis, ChIP-seq, nascent RNA-seq/PRO-seq and siRNA epistasis across two companion studies

    PMID:37329882 PMID:37329883

    Open questions at the time
    • How transcript length/U1 occupancy is sensed mechanistically unresolved
    • Structural basis of the ARS2-ZC3H4 SLiM interaction not solved
  18. 2024 Medium

    Linked ARS2 to T-cell biology, showing CD28 costimulation induces ARS2 to reinforce splicing-factor recruitment and reprogram alternative splicing, including a PKM1-to-PKM2 switch driving metabolic rewiring.

    Evidence siRNA knockdown, RNA-seq splicing analysis, flow cytometry, metabolic assays and splicing-factor Co-IP

    PMID:38233562

    Open questions at the time
    • Direct ARS2-splicing-factor contacts not structurally defined
    • Whether splicing role is co-transcriptional via CBC unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ARS2 hub dynamically selects among its mutually exclusive partners (PHAX, NELF-E, NCBP3, FLASH, ZC3H4) on individual transcripts in real time, and which intrinsic DNA-binding determinant underlies its enhancer transcription-factor activity, remain unresolved.
  • No structural model of the full ARS2 complex switching cycle
  • DNA-recognition domain for direct enhancer binding unmapped
  • Quantitative rules governing decay versus processing outcomes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0060090 molecular adaptor activity 4 GO:0003677 DNA binding 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2
Partners
FLASHMTR4NCBP1/CBP80-CBCNCBP3NELF-EPHAXZC3H18ZC3H4
Complex memberships
CBC-ARS2-NCBP3CBC-ARS2-PHAX (CBCAP)restrictor (ZC3H4-WDR82-ARS2)

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 Drosophila Ars2 physically interacts with Dcr-2 and modulates its activity in vitro, and is required for siRNA-mediated silencing; it also interacts with the Microprocessor and stabilizes pri-miRNAs, playing an essential role in miRNA-mediated silencing. Co-immunoprecipitation, in vitro activity assay, RNAi knockdown in cells and flies with viral susceptibility and small RNA readouts Cell High 19632183
2009 Mammalian Ars2, as a component of the nuclear cap-binding complex (CBC), is required for miRNA biogenesis and primary miRNA processing in the nucleus; depletion impairs miRNA-mediated repression and reduces levels of miR-21, let-7, and miR-155. Ars2 depletion (shRNA/siRNA) with miRNA northern blot, luciferase reporter assays for miRNA-mediated repression, nuclear fractionation and pri-miRNA processing assays Cell High 19632182
2013 Human ARS2 forms the CBCAP complex with CBC and PHAX, stimulates PHAX binding to the CBC, enhances snRNA 3'-end processing, and promotes cap-proximal polyadenylation sites; it functions partly through the mRNA 3'-end cleavage factor CLP1 which connects to RNA Pol II via PCF11. Recombinant protein reconstitution of CBC-ARS2-PHAX complex, biochemical co-immunoprecipitation, in vivo 3'-end processing assays, ChIP Nature structural & molecular biology High 24270878
2012 Ars2 regulates replication-dependent histone mRNA 3'-end formation: it physically associates with histone mRNAs and the noncoding RNA 7SK; its depletion causes a significant reduction in correctly processed (non-polyadenylated) histone mRNAs and an increase in polyadenylated histone transcripts. Knockdown of 7SK enhances the ratio of cleaved to polyadenylated histone transcripts in an Ars2-dependent manner. RIP (RNA immunoprecipitation), qRT-PCR, siRNA knockdown, 3'-end processing assays Molecular cell High 22244333
2011 Ars2 (Srrt) maintains neural stem cell identity by directly binding the NSC enhancer of Sox2 and transcriptionally activating Sox2 expression; this activity is RNA-independent and requires a specific conserved DNA sequence within the Sox2 enhancer. This NSC self-renewal function is retained in Drosha and Dicer1 knockout NSCs, indicating it is independent of miRNA biogenesis. Chromatin immunoprecipitation (ChIP), gel-shift assay (EMSA), conditional knockout mice, ex vivo neurosphere assay, Sox2 rescue experiments Nature High 22198669
2018 Human ARS2 crystal structure reveals an RRM domain absent in the plant homologue SERRATE. Biochemical and cellular interactome data identify regions critical for interactions with FLASH (histone mRNA biogenesis), NCBP3 (mRNA export), and single-stranded RNA. FLASH and NCBP3 have overlapping binding sites on ARS2; CBC-ARS2-NCBP3 form a ternary complex mutually exclusive with CBC-ARS2-PHAX. X-ray crystallography, biochemical pulldown, biophysical binding assays, mass spectrometry interactome, mutagenesis Nature communications High 29703953
2017 ARS2 depletion causes transcriptional read-through at gene terminators and negatively impacts levels of promoter-proximal RNA Pol II at protein-coding genes. ARS2 is a general suppressor of pervasive transcription, functioning in transcription termination-coupled RNA turnover at snRNA, replication-dependent histone, promoter upstream transcript, and enhancer RNA loci. ARS2 physically interacts with ZC3H18, and ARS2 is also involved in transcription termination within first introns of protein-coding genes. GRO-seq, RNA-seq, ChIP-seq, ARS2 knockdown (siRNA), ZC3H18 and exosome subunit depletion for epistasis Nucleic acids research High 28973446
2017 The C-terminal peptides of NELF-E and ARS2 bind identically to CBC; affinity of both interactions is enhanced when CBC is bound to a cap analogue. PHAX forms a complex with CBC and ARS2, whereas NELF-E binding to CBC is incompatible with PHAX, defining two mutually exclusive complexes: CBC-NELF-E and CBC-ARS2-PHAX acting in earlier and later phases of transcription respectively. X-ray crystallography of CBC-NELF-E complex, biochemical binding assays, isothermal titration calorimetry, mutagenesis Nature communications High 29101316
2023 A conserved basic domain of ARS2 binds an acidic-rich short linear motif (SLiM) in ZC3H4, recruiting ZC3H4 to chromatin to elicit RNA Pol II termination independent of CPA and Integrator pathways. ZC3H4 directly connects to the nuclear exosome targeting (NEXT) complex to facilitate rapid degradation of nascent RNA. At CPA-instructed termination sites, ARS2 exclusively participates in post-transcriptional RNA decay. Co-immunoprecipitation, ChIP-seq, siRNA knockdown epistasis, nascent RNA-seq, domain mapping/mutagenesis Molecular cell High 37329882
2023 ZC3H4 additionally associates with ARS2 and the nuclear exosome targeting (NEXT) complex; the domains of ZC3H4 contacting ARS2 and WDR82 are required for ncRNA restriction. ZC3H4, WDR82, and ARS2 co-transcriptionally control an overlapping population of ncRNAs. PNUTS enables restrictor (ZC3H4-WDR82-ARS2) function, and U1 snRNA shields longer protein-coding transcripts from restrictor and PNUTS. Co-immunoprecipitation, domain mutagenesis, nascent RNA-seq, PRO-seq, siRNA knockdown epistasis Molecular cell High 37329883
2020 ARS2 knockdown inhibits the association between NEAT1 lncRNA and the mammalian cleavage factor I (CFIm), which produces the shorter NEAT1_1 isoform. Knockdown of ARS2 leads to preferential stabilization and elevated levels of NEAT1_2, resulting in increased numbers of paraspeckles. siRNA knockdown, RIP (NEAT1-CFIm co-immunoprecipitation), fluorescence microscopy for paraspeckle counting, qRT-PCR Molecular and cellular biology Medium 31818879
2007 Mouse ARS2 protein is predominantly localized to the nucleus; ARS2-null embryos die around implantation with increased apoptosis and failure to proliferate, establishing ARS2 as essential for early mammalian development and an essential cellular process related to RNA metabolism. Conditional knockout mice, immunofluorescence localization, in vitro blastocyst culture, TUNEL apoptosis assay Molecular and cellular biology Medium 18086880
2015 ARS2 domain mutagenesis reveals: the DUF3546 and zinc finger (ZnF) domains are required for association with microRNA and replication-dependent histone mRNA; the ZnF domain mediates interaction with FLASH; the Mid domain is required for DROSHA interaction and miRNA biogenesis; the unstructured C-terminus is required for interaction with CBP20; the RRM domain (metazoan-specific) is required for cell cycle progression and FLASH binding. Site-directed mutagenesis, co-immunoprecipitation, RNA immunoprecipitation, cell cycle analysis (flow cytometry) Molecular and cellular biology Medium 26303529
2020 ARS2 directly activates its transcriptional target MGLL (encoding MAGL) in glioblastoma stem cells (GSCs), leading to prostaglandin E2 (PGE2) production, β-catenin activation in GSCs, and M2-like TAM polarization. ChIP, luciferase reporter assay, siRNA/shRNA knockdown, xenograft mouse model Nature communications Medium 32532977
2020 ZnF domain of ARS2 is essential for RNA decay triggered by ARS2 and is required for interaction with the PAXT-associated RNA helicase MTR4, whereas the C-terminal CBC-binding region is dispensable when ARS2 is directly tethered to RNA. Tethering assay, co-immunoprecipitation, siRNA knockdown of ARS2 domains/mutants, RNA reporter decay assay Nucleic acids research Medium 32463452
2020 Pir2/ARS2 in fission yeast associates with splicing factors and lncRNAs containing cryptic introns to recruit RNA processing and chromatin-modifying activities involved in gene silencing. Human ARS2 also interacts with splicing factors, suggesting a conserved mechanism. Co-immunoprecipitation in S. pombe, RNA-seq, ChIP-seq, genetic epistasis with splicing factor mutants Nature communications Medium 32415063
2022 In C. elegans, ARS2 (as part of CBC-ARS2) interacts with the novel nematode-specific protein SNA-3, which bridges the SL1 snRNP to CBC-ARS2 and other RNA metabolism factors; this interaction is required for SL1 trans-splicing. GFP-tagged SNA-1 immunoprecipitation, RIP-Seq, mass spectrometry, yeast two-hybrid, immunoprecipitation, localization microscopy Nucleic acids research Medium 35736244
2024 CD28 costimulation upregulates ARS2 in CD8+ T cells, and ARS2 reinforces splicing factor recruitment to pre-mRNAs, affecting approximately one-third of T-cell activation-induced alternative splicing events. Among these, the CD28-ARS2 axis suppresses expression of the M1 isoform of pyruvate kinase in favor of PKM2, driving metabolic reprogramming independently of CD28-PI3K pathway activation. siRNA knockdown of ARS2, RNA-seq (alternative splicing analysis), flow cytometry, metabolic assays, co-immunoprecipitation of splicing factors Cellular & molecular immunology Medium 38233562
2018 Depletion of Ars2 in acute myeloid leukemia cells suppressed the interaction of Ars2 with CBC and led to alterations in miRNA processing; Ars2 depletion reduced levels of miR-6734-3p, resulting in upregulation of p27 and cell cycle arrest at G1 phase. Co-immunoprecipitation (Ars2-CBC), shRNA knockdown, miRNA qRT-PCR, flow cytometry (cell cycle), in vivo xenograft Leukemia Medium 30518811
2020 In vivo conditional knockout of murine Ars2 reveals it is required for embryonic neural stem cell proliferation and for terminal differentiation of post-mitotic neurons. Adult-specific deletion compromises hippocampal neurogenesis. ChIP-seq shows Ars2 preferentially occupies DNA enhancers in NSCs and colocalizes broadly with SOX2; Ars2 chromatin association is markedly reduced following NSC differentiation. Conditional knockout mice (embryonic and adult), ChIP-seq, behavioral assays, immunofluorescence Development Medium 31969356
2011 Ars2 depletion in cholangiocarcinoma cells decreased miR-21 levels and increased PTEN and PDCD4 protein levels; this increase was reversed by miR-21 mimic co-transfection, placing Ars2 upstream of miR-21 in regulation of its targets. shRNA knockdown, miRNA qRT-PCR, Western blot, mimic transfection epistasis Molecular carcinogenesis Low 22213145

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell 690 1657403
1997 The function and regulation of cut expression on the wing margin of Drosophila: Notch, Wingless and a dominant negative role for Delta and Serrate. Development (Cambridge, England) 367 9108365
1995 Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing. Development (Cambridge, England) 355 8575321
1996 Delta is a ventral to dorsal signal complementary to Serrate, another Notch ligand, in Drosophila wing formation. Genes & development 301 8600026
1996 A chick homologue of Serrate and its relationship with Notch and Delta homologues during central neurogenesis. Developmental biology 284 8631496
2006 SERRATE: a new player on the plant microRNA scene. EMBO reports 278 16977334
1998 Cell fate choices and the expression of Notch, Delta and Serrate homologues in the chick inner ear: parallels with Drosophila sense-organ development. Development (Cambridge, England) 260 9806914
1994 Sequence of C. elegans lag-2 reveals a cell-signalling domain shared with Delta and Serrate of Drosophila. Nature 236 8139658
1997 Serrate-mediated activation of Notch is specifically blocked by the product of the gene fringe in the dorsal compartment of the Drosophila wing imaginal disc. Development (Cambridge, England) 217 9247339
2008 A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition. Nature structural & molecular biology 203 18660822
1990 The gene Serrate encodes a putative EGF-like transmembrane protein essential for proper ectodermal development in Drosophila melanogaster. Genes & development 199 2125287
1994 The Serrate locus of Drosophila and its role in morphogenesis of the wing imaginal discs: control of cell proliferation. Development (Cambridge, England) 198 8162853
1996 Jagged2: a serrate-like gene expressed during rat embryogenesis. Developmental biology 195 8948600
2003 A Serrate-expressing signaling center controls Drosophila hematopoiesis. Genes & development 184 12569125
2009 Ars2 regulates both miRNA- and siRNA- dependent silencing and suppresses RNA virus infection in Drosophila. Cell 178 19632183
2009 Ars2 links the nuclear cap-binding complex to RNA interference and cell proliferation. Cell 171 19632182
1991 The Drosophila gene Serrate encodes an EGF-like transmembrane protein with a complex expression pattern in embryos and wing discs. Development (Cambridge, England) 169 1840519
2005 Two distinct E3 ubiquitin ligases have complementary functions in the regulation of delta and serrate signaling in Drosophila. PLoS biology 147 15760269
1996 The intracellular deletions of Delta and Serrate define dominant negative forms of the Drosophila Notch ligands. Development (Cambridge, England) 142 8756291
2005 The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta. Development (Cambridge, England) 140 15829515
1997 Mouse Serrate-1 (Jagged-1): expression in the developing tooth is regulated by epithelial-mesenchymal interactions and fibroblast growth factor-4. Development (Cambridge, England) 138 9108364
2013 CBC-ARS2 stimulates 3'-end maturation of multiple RNA families and favors cap-proximal processing. Nature structural & molecular biology 136 24270878
1997 Secreted forms of DELTA and SERRATE define antagonists of Notch signaling in Drosophila. Development (Cambridge, England) 124 9310338
2020 ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages. Nature communications 120 32532977
2018 SWI2/SNF2 ATPase CHR2 remodels pri-miRNAs via Serrate to impede miRNA production. Nature 119 29769717
1999 Composite signalling from Serrate and Delta establishes leg segments in Drosophila through Notch. Development (Cambridge, England) 115 10357942
1997 An intrinsic dominant negative activity of serrate that is modulated during wing development in Drosophila. Developmental biology 112 9281342
1998 Interactions among Delta, Serrate and Fringe modulate Notch activity during Drosophila wing development. Development (Cambridge, England) 111 9655817
2000 Serrate and Notch specify cell fates in the heart field by suppressing cardiomyogenesis. Development (Cambridge, England) 106 10934030
1999 Ligand-receptor interactions and trans-endocytosis of Delta, Serrate and Notch: members of the Notch signalling pathway in Drosophila. Journal of cell science 100 10504334
2006 Role of conserved intracellular motifs in Serrate signalling, cis-inhibition and endocytosis. The EMBO journal 96 17006545
1998 Delta and Serrate are redundant Notch ligands required for asymmetric cell divisions within the Drosophila sensory organ lineage. Genes & development 93 9553038
2012 A mutation in EGF repeat-8 of Notch discriminates between Serrate/Jagged and Delta family ligands. Science (New York, N.Y.) 81 23197537
2012 Ars2 promotes proper replication-dependent histone mRNA 3' end formation. Molecular cell 72 22244333
2011 Ars2 maintains neural stem-cell identity through direct transcriptional activation of Sox2. Nature 71 22198669
1993 Genetic and molecular characterization of a Notch mutation in its Delta- and Serrate-binding domain in Drosophila. Proceedings of the National Academy of Sciences of the United States of America 71 8483919
1997 A dominant-negative form of Serrate acts as a general antagonist of Notch activation. Development (Cambridge, England) 69 9310337
1995 Serrate expression can functionally replace Delta activity during neuroblast segregation in the Drosophila embryo. Development (Cambridge, England) 69 7720588
1997 Asymmetric expression of Notch/Delta/Serrate is associated with the anterior-posterior axis of feather buds. Developmental biology 63 9245521
2016 miRNA863-3p sequentially targets negative immune regulator ARLPKs and positive regulator SERRATE upon bacterial infection. Nature communications 57 27108563
2000 Structural requirements for notch signalling with delta and serrate during the development and patterning of the wing disc of Drosophila. Development (Cambridge, England) 55 10862754
2018 Structural analysis of human ARS2 as a platform for co-transcriptional RNA sorting. Nature communications 52 29703953
2017 ARS2 is a general suppressor of pervasive transcription. Nucleic acids research 52 28973446
2006 Lobe and Serrate are required for cell survival during early eye development in Drosophila. Development (Cambridge, England) 52 17090721
1995 Phenotypic and molecular characterization of SerD, a dominant allele of the Drosophila gene Serrate. Genetics 52 7705624
2011 Ars2 is overexpressed in human cholangiocarcinomas and its depletion increases PTEN and PDCD4 by decreasing microRNA-21. Molecular carcinogenesis 50 22213145
1999 Hox genes differentially regulate Serrate to generate segment-specific structures. Development (Cambridge, England) 50 10101132
2007 ARS2 is a conserved eukaryotic gene essential for early mammalian development. Molecular and cellular biology 47 18086880
1998 Dissection of cis-regulatory elements of the Drosophila gene Serrate. Development genes and evolution 45 9716725
1994 High-efficiency transformation of Pichia stipitis based on its URA3 gene and a homologous autonomous replication sequence, ARS2. Applied and environmental microbiology 45 7811063
2015 2,3,5,6-Tetramethylpyrazine (TMP) down-regulated arsenic-induced heme oxygenase-1 and ARS2 expression by inhibiting Nrf2, NF-κB, AP-1 and MAPK pathways in human proximal tubular cells. Archives of toxicology 43 26404762
2017 Structural basis for mutually exclusive co-transcriptional nuclear cap-binding complexes with either NELF-E or ARS2. Nature communications 42 29101316
1981 Characterization of a yeast replication origin (ars2) and construction of stable minichromosomes containing cloned yeast centromere DNA (CEN3). Gene 40 7028571
2023 A restrictor complex of ZC3H4, WDR82, and ARS2 integrates with PNUTS to control unproductive transcription. Molecular cell 39 37329883
2020 Degradation of SERRATE via ubiquitin-independent 20S proteasome to survey RNA metabolism. Nature plants 39 32690892
2023 ARS2 instructs early transcription termination-coupled RNA decay by recruiting ZC3H4 to nascent transcripts. Molecular cell 38 37329882
2019 Antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate gum resin in CCl4-induced hepatotoxicity. Experimental and therapeutic medicine 38 32010304
2020 MAC5, an RNA-binding protein, protects pri-miRNAs from SERRATE-dependent exoribonuclease activities. Proceedings of the National Academy of Sciences of the United States of America 35 32887800
2013 An extracellular region of Serrate is essential for ligand-induced cis-inhibition of Notch signaling. Development (Cambridge, England) 35 23571220
1998 Ectopic expression of lunatic Fringe leads to downregulation of Serrate-1 in the developing chick neural tube; analysis using in ovo electroporation transfection technique. FEBS letters 35 9600262
1996 Distinct functions of the Drosophila genes Serrate and Delta revealed by ectopic expression during wing development. Development genes and evolution 33 24173462
2003 Adaptive evolution of the water stress-induced gene Asr2 in Lycopersicon species dwelling in arid habitats. Molecular biology and evolution 31 12949146
1996 Isolation of a novel chick homolog of Serrate and its coexpression with C-Notch-1 in chick development. The International journal of developmental biology 26 9032014
2021 ARS2/SRRT: at the nexus of RNA polymerase II transcription, transcript maturation and quality control. Biochemical Society transactions 25 34060620
2020 Apple SERRATE negatively mediates drought resistance by regulating MdMYB88 and MdMYB124 and microRNA biogenesis. Horticulture research 25 32637126
2013 Molecular basis for Jagged-1/Serrate ligand recognition by the Notch receptor. The Journal of biological chemistry 25 23339193
1999 Phylogenetic analysis of vertebrate and invertebrate Delta/Serrate/LAG-2 (DSL) proteins. Molecular phylogenetics and evolution 25 10191075
1997 Beaded of Goldschmidt, an antimorphic allele of Serrate, encodes a protein lacking transmembrane and intracellular domains. Genetics 25 9071590
2022 Pro-inflammatory cytokine molecules from Boswellia serrate suppresses lipopolysaccharides induced inflammation demonstrated in an in-vivo zebrafish larval model. Molecular biology reports 24 35716287
2020 ARS2 Regulates Nuclear Paraspeckle Formation through 3'-End Processing and Stability of NEAT1 Long Noncoding RNA. Molecular and cellular biology 23 31818879
2015 Mutagenesis of ARS2 Domains To Assess Possible Roles in Cell Cycle Progression and MicroRNA and Replication-Dependent Histone mRNA Biogenesis. Molecular and cellular biology 22 26303529
2000 The serrate leaf margined Juniperus (Section Sabina) of the western hemisphere: systematics and evolution based on leaf essential oils and Random Amplified Polymorphic DNAs (RAPDs). Biochemical systematics and ecology 20 10996262
2024 SERRATE drives phase separation behaviours to regulate m6A modification and miRNA biogenesis. Nature cell biology 19 39472512
2023 SERRATE: a key factor in coordinated RNA processing in plants. Trends in plant science 19 37019716
2013 A Serrate-Notch-Canoe complex mediates essential interactions between glia and neuroepithelial cells during Drosophila optic lobe development. Journal of cell science 18 23970418
2011 Isolation and characterization of cDNAs encoding Ars2 and Pasha homologues, two components of the RNA interference pathway in Litopenaeus vannamei. Fish & shellfish immunology 18 22155278
2004 The intracellular domain of X-Serrate-1 is cleaved and suppresses primary neurogenesis in Xenopus laevis. Mechanisms of development 18 15172688
2001 X-Serrate-1 is involved in primary neurogenesis in Xenopus laevis in a complementary manner with X-Delta-1. Development genes and evolution 18 11685570
2018 Depletion of Ars2 inhibits cell proliferation and leukemogenesis in acute myeloid leukemia by modulating the miR-6734-3p/p27 axis. Leukemia 17 30518811
2020 Conserved protein Pir2ARS2 mediates gene repression through cryptic introns in lncRNAs. Nature communications 16 32415063
2020 Mapping domains of ARS2 critical for its RNA decay capacity. Nucleic acids research 16 32463452
2024 The METHYLTRANSFERASE B-SERRATE interaction mediates the reciprocal regulation of microRNA biogenesis and RNA m6A modification. Journal of integrative plant biology 15 39206840
2018 Serrate/Notch Signaling Regulates the Size of the Progenitor Cell Pool in Drosophila Imaginal Rings. Genetics 15 29773559
2005 Serrate-Notch signaling defines the scope of the initial denticle field by modulating EGFR activation. Developmental biology 15 16125166
2024 CD8+ T cell metabolic flexibility elicited by CD28-ARS2 axis-driven alternative splicing of PKM supports antitumor immunity. Cellular & molecular immunology 14 38233562
2021 Identification of the atypically modified autoantigen Ars2 as the target of B-cell receptors from activated B-cell-type diffuse large B-cell lymphoma. Haematologica 14 32675228
2014 An improved ARS2-derived nuclear reporter enhances the efficiency and ease of genetic engineering in Chlamydomonas. Biotechnology journal 14 25224580
2002 Cysteine-rich region of X-Serrate-1 is required for activation of Notch signaling in Xenopus primary neurogenesis. The International journal of developmental biology 14 12533029
1998 Positive and negative control of Serrate expression during early development of the Drosophila wing. Mechanisms of development 14 9767116
2009 Ars2 and the Cap-Binding Complex Team up for Silencing. Cell 13 19632172
2008 Nucleotide polymorphism in the drought responsive gene Asr2 in wild populations of tomato. Genetica 13 18636230
2018 The RNA binding protein Ars2 supports hematopoiesis at multiple levels. Experimental hematology 12 29775646
2007 dAP-2 and defective proventriculus regulate Serrate and Delta expression in the tarsus of Drosophila melanogaster. Genome 12 17893729
2018 Ars2 promotes cell proliferation and tumorigenicity in glioblastoma through regulating miR-6798-3p. Scientific reports 10 30349053
2009 Fly antiviral RNA silencing and miRNA biogenesis claim ARS2. Cell host & microbe 10 19683674
2025 A plant bunyaviral protein disrupts SERRATE phase separation to modulate microRNA biogenesis during viral pathogenesis. Nature communications 9 40615422
2022 Nuclear and Membrane Receptors for Sex Steroids Are Involved in the Regulation of Delta/Serrate/LAG-2 Proteins in Rodent Sertoli Cells. International journal of molecular sciences 9 35216398
2020 Regulation of embryonic and adult neurogenesis by Ars2. Development (Cambridge, England) 9 31969356
2022 A novel, essential trans-splicing protein connects the nematode SL1 snRNP to the CBC-ARS2 complex. Nucleic acids research 8 35736244
2018 To be serrate or pinnate: diverse leaf forms of yarrows (Achillea) are linked to differential expression patterns of NAM genes. Annals of botany 7 29267935

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