SERRATE (SE, At2g27100) is a 720-residue nuclear protein of the conserved ARS2 family (metazoan ortholog ARS2/SRRT). It has a structured core (roughly residues 194-543) carrying a single non-canonical C2H2-type zinc finger, flanked by long intrinsically disordered N- and C-terminal regions. SE is a cofactor of the plant microprocessor. It binds the RNase III enzyme DICER-LIKE1 (DCL1) and the dsRNA-binding protein HYPONASTIC LEAVES1 (HYL1/DRB1), and it binds RNA. With these partners it raises the rate and accuracy of DCL1 cleavage of primary and precursor miRNAs. SE is required for the accumulation of most miRNAs and, indirectly, of miRNA-triggered trans-acting siRNAs. SE forms liquid-like condensates that recruit DCL1, HYL1 and pri-miRNAs, and it is needed to form nuclear dicing bodies. It also acts as a scaffold that brings other proteins to the processing complex or its RNA substrates: the phosphatase CPL1 (to dephosphorylate HYL1), the chromatin remodeler CHR2/BRM, and the NEXT exosome-targeting complex that degrades pri-miRNAs. Like ARS2, SE associates with the nuclear cap-binding complex (CBP20/CBP80). Together with this complex it promotes pre-mRNA splicing and affects alternative 5' splice site choice in first introns. Chromatin-bound SE also associates with RNA polymerase II and promotes transcription of many intronless, stress-responsive genes. SE is located in the nucleoplasm, mainly in nuclear speckles, and transiently in dicing bodies. Null alleles are embryo-lethal. Weak alleles (se-1 to se-3) have serrated, curled or polarity-defective leaves, altered phyllotaxy and altered phase transitions. These defects largely reflect reduced miRNA regulation of developmental regulators such as the HD-ZIP III genes.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000381 regulation of alternative mRNA splicing, via spliceosome | IMP PMID:24137006 The SERRATE protein is involved in alternative splicing in A... | ACCEPT | Summary: SE mutants (se-1) show alternative splicing changes that overlap those of cbp20/cbp80 mutants, mainly in 5' splice site choice of first introns. SE binds both CBC subunits and acts with CBC in this role, separately from its role in miRNA processing. Reason: High-resolution RT-PCR splicing panels in se-1 (full text available) show CBC-like changes in alternative splicing that differ from those in hyl1-2 or dcl1-7. So this is a direct SE/CBC function, not a downstream effect of reduced miRNA levels. It is part of the conserved CBC-associated role of SE/ARS2 in RNA processing. Supporting Evidence: PMID:24137006 AtSE influences AS in a similar way to the cap-binding complex (CBC), preferentially affecting selection of 5' splice site of first introns PMID:24137006 Thus, the role of SERRATE in AS regulation is distinct from that of HYL1 and DCL1, and is similar to the regulation of AS in which CBC is involved. |
| GO:0003677 DNA binding | ISS PMID:11402159 The arabidopsis serrate gene encodes a zinc-finger protein r... | REMOVE | Summary: This ISS annotation comes from the original cloning paper. That paper noticed a C2H2 zinc finger and speculated that SE acts through chromatin modification. No later work has shown that SE binds DNA directly. Reason: The single SE zinc finger is non-canonical. Structural and biochemical work shows that it, together with the N-terminal and core regions, binds RNA and the protein DCL1. It does not bind DNA. SE does associate with chromatin, but through RNA polymerase II complexes rather than direct DNA binding (PMID:30152752). The inference from the zinc-finger motif is not supported by later evidence. Supporting Evidence: PMID:11402159 suggests a role for the SE gene product in regulating changes in gene expression via chromatin modification PMID:23921632 SE uses its N-terminal domain to bind to RNA and requires both N-terminal and ZnF domains to bind to DCL1. PMID:30152752 Chromatin-bound SE liaised with paused and elongating polymerase II complexes and promoted their association with intronless target genes. |
| GO:0003700 DNA-binding transcription factor activity | ISS PMID:11118137 Arabidopsis transcription factors: genome-wide comparative a... | REMOVE | Summary: The genome-wide transcription-factor census counted SE as a transcription factor because it has a C2H2 zinc finger. SE is an RNA-processing cofactor and has never been shown to be a sequence-specific DNA-binding transcription factor. Reason: The cited paper is a motif-based genome census (abstract only). It does not report any experiment on SE. Later work places SE in pri-miRNA processing, CBC-linked splicing and Pol II-associated transcription of intronless genes. In none of these does SE act as a sequence-specific DNA-binding transcription factor. Supporting Evidence: PMID:11118137 Arabidopsis transcription factors that belong to families common to all eukaryotes do not share significant similarity with those of the other kingdoms beyond the conserved DNA binding domains PMID:18632569 We show that recombinant HYL1 and SE proteins accelerate the rate of DCL1-mediated cleavage of pre- and pri-miR167b substrates and promote accurate processing. |
| GO:0003723 RNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: SE binds RNA directly. Recombinant SE binds pri-miRNA through its N-terminal region, and the zinc-finger/C-terminal region contributes to binding of miRNA precursors. RNA binding is a family-wide ARS2 property. Reason: The IBA placement fits direct in vitro RNA-binding data for Arabidopsis SE. SE/ARS2 proteins bind many capped Pol II transcripts, not only pri-miRNAs, so the general term is the right level for the family assertion. Supporting Evidence: PMID:23921632 SE uses its N-terminal domain to bind to RNA PMID:21685453 in vitro RNA binding and in vivo mutant rescue experiments suggest that the non-canonical zinc-finger domain coupled with C-terminal tail binds miRNA precursors |
| GO:0005515 protein binding | IPI PMID:16889646 SERRATE is a novel nuclear regulator in primary microRNA pro... | REMOVE | Summary: SE binds HYL1/DRB1 (O04492). This is a real interaction within the plant microprocessor. Reason: Removed under the protein-binding policy because the bare term is uninformative. The interaction itself is not disputed. The functional result of SE binding to the processing machinery is covered by the NEW ribonuclease activator activity row (stimulation of DCL1) and by protein-macromolecule adaptor activity. Supporting Evidence: PMID:16889646 We further demonstrate that SE is localized in the nucleus and interacts physically with HYL1. |
| GO:0005515 protein binding | IPI PMID:20462493 Structure of Arabidopsis HYPONASTIC LEAVES1 and its molecula... | REMOVE | Summary: SE-HYL1 interaction reported in the HYL1 structure paper. Reason: Removed under the protein-binding policy because the bare term is uninformative. The interaction itself is not disputed. More informative terms elsewhere in this review cover what SE does in the microprocessor. Supporting Evidence: PMID:20462493 In plants, both pri-miRNA processing and pre-miRNA processing occur inside the nucleus by a complex comprising of at least three protein subunits: DCL1 (an RNase III protein), HYL1 (a dsRNA-binding protein), and SERRATE (SE; a zinc-finger-domain protein). |
| GO:0005515 protein binding | IPI PMID:23141542 Fast-forward genetics identifies plant CPL phosphatases as r... | MODIFY | Summary: SE binds HYL1 and acts as the scaffold that brings the phosphatase CPL1 to HYL1, so that HYL1 is dephosphorylated and becomes fully active. Reason: This paper shows that SE bridges two proteins (CPL1 and HYL1). That is protein-macromolecule adaptor activity, which is more informative than bare protein binding and agrees with the IBA adaptor-activity row. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:23141542 In the miRNA processing complex, SE functions as a scaffold to mediate CPL1 interaction with HYL1, which needs to be dephosphorylated for optimal activity. |
| GO:0005515 protein binding | IPI PMID:23141542 Fast-forward genetics identifies plant CPL phosphatases as r... | MODIFY | Summary: SE binds CPL1 (Q5YDB6) and links it to HYL1 in the miRNA processing complex. Reason: The SE-CPL1 interaction is the recruitment half of the SE scaffold function described in this paper. It is better captured as protein-macromolecule adaptor activity. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:23141542 In the miRNA processing complex, SE functions as a scaffold to mediate CPL1 interaction with HYL1 |
| GO:0005515 protein binding | IPI PMID:26227967 The RNA-binding protein HOS5 and serine/arginine-rich protei... | REMOVE | Summary: SE interacts with the SR protein RS40 (P92965) in nuclear splicing speckles (BiFC, co-IP). Reason: Removed under the protein-binding policy because the bare term is uninformative. The interaction itself is not disputed. The paper does not establish a more specific molecular function for SE in this interaction. Supporting Evidence: PMID:26227967 all of these splicing-related factors directly interact with both HYL1 and SE in nuclear splicing speckles |
| GO:0005515 protein binding | IPI PMID:26227967 The RNA-binding protein HOS5 and serine/arginine-rich protei... | REMOVE | Summary: SE interacts with the SR protein RS41 (P92966) in nuclear splicing speckles. Reason: Removed under the protein-binding policy because the bare term is uninformative. The interaction itself is not disputed. Supporting Evidence: PMID:26227967 all of these splicing-related factors directly interact with both HYL1 and SE in nuclear splicing speckles |
| GO:0005515 protein binding | IPI PMID:26227967 The RNA-binding protein HOS5 and serine/arginine-rich protei... | REMOVE | Summary: SE interacts with HOS5/RCF3 (Q8W4B1) in nuclear splicing speckles. Reason: Removed under the protein-binding policy because the bare term is uninformative. The interaction itself is not disputed. Supporting Evidence: PMID:26227967 all of these splicing-related factors directly interact with both HYL1 and SE in nuclear splicing speckles |
| GO:0005515 protein binding | IPI PMID:29769717 SWI2/SNF2 ATPase CHR2 remodels pri-miRNAs via Serrate to imp... | REMOVE | Summary: SE-HYL1 interaction detected in the CHR2/BRM study. Reason: Removed under the protein-binding policy because the bare term is uninformative. The interaction itself is not disputed. The functional result is captured by other terms in this review. Supporting Evidence: PMID:29769717 CHR2 (also known as BRM), the ATPase subunit of the large switch/sucrose non-fermentable (SWI/SNF) complex, is a partner of the Microprocessor component Serrate (SE) |
| GO:0005515 protein binding | IPI PMID:29769717 SWI2/SNF2 ATPase CHR2 remodels pri-miRNAs via Serrate to imp... | MODIFY | Summary: SE binds CHR2/BRM (Q6EVK6). CHR2 reaches pri-miRNAs through this interaction and then remodels their secondary structure, which inhibits processing. Reason: The paper (abstract only) shows that SE recruits CHR2 to its RNA substrate, and that this post-transcriptional inhibition requires direct binding to SE. Bringing a protein into contact with an RNA substrate is protein-macromolecule adaptor activity, which is more informative than bare protein binding. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:29769717 Direct interaction with SE is required for post-transcriptional inhibition of miRNA accumulation by CHR2 but not for its transcriptional activity. PMID:29769717 We conclude that CHR2 accesses pri-miRNAs through SE and remodels their secondary structures, preventing downstream processing by DCL1 and HYL1. |
| GO:0005515 protein binding | IPI PMID:29982637 SMA1, a homolog of the splicing factor Prp28, has a multifac... | MODIFY | Summary: SE co-immunoprecipitates with DCL1 (AT1G01040) and with the DEAD-box helicase SMA1 (AT2G33730). Reason: Bare protein binding is uninformative, but this row records SE with DCL1 (AT1G01040) and SMA1 (AT2G33730), and the full text supports the adaptor reading used for the SE-HYL1/CPL1 rows from PMID:23141542. The paper describes the DCL1 complex as DCL1, SE and HYL1, with SE and HYL1 improving the efficiency and accuracy of DCL1 cleavage. Its own BiFC and RNase-insensitive co-IP experiments show SMA1 associating with both DCL1 and SE, an accessory factor docking onto the SE-containing DCL1 complex. SE binding to DCL1 within this complex is the DCL1 half of the HYL1-DCL1 bridge in core_functions, so protein-macromolecule adaptor activity (GO:0030674), which SE carries by IBA, describes it. The SE-DCL1 contact itself is stated in the introduction from earlier work rather than re-tested here; stimulation of DCL1 is captured separately by the NEW ribonuclease activator activity row (PMID:18632569). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:29982637 pri-miRNAs are processed by the DICER-LIKE 1 (DCL1) complex, which is composed of the RNase III enzyme DCL1, the Zinc-finger protein SERRATE (SE) and the double-stranded RNA (dsRNA)-binding protein HYPONASTIC LEAVES 1 (HYL1) PMID:29982637 Among DCL1 components, DCL1 directly cleaves pri-miRNAs while SE and HYL1 improve the efficiency and accuracy of DCL1 activity PMID:29982637 After IP, both DCL1 and SE were detected in the GFP-SMA1 precipitates but not in the GFP precipitates PMID:29982637 SMA1 interacts with the DCL1 complex and positively influences pri-miRNA processing. |
| GO:0005515 protein binding | IPI PMID:32449937 SERRATE interacts with the nuclear exosome targeting (NEXT) ... | MODIFY | Summary: SE interacts with components of the NEXT complex (RBM7 and the ZCCHC8 zinc-knuckle proteins) and recruits NEXT/HEN2 to pri-miRNAs and other RNAs for nuclear exosome degradation. Reason: The paper (full text) presents SE as recruiting the NEXT complex to its RNA targets. This is an adaptor function and matches the role of human ARS2 in recruiting RNA-decay machinery to CBC-bound RNAs. Protein-macromolecule adaptor activity is more informative than bare protein binding. Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:32449937 SE regulates miRNA biogenesis through its double contribution in promoting miRNA processing but also pri-miRNA degradation through the recruitment of the NEXT complex |
| GO:0005515 protein binding | IPI PMID:34449907 Serrate-Associated Protein 1, a splicing-related protein, pr... | REMOVE | Summary: SE interacts with SEAP1 (AT4G24270), a conserved splicing-related protein that associates with the DCL1 complex. Reason: Removed under the protein-binding policy because the bare term is uninformative. The interaction itself is not disputed. The paper does not define a more specific molecular function for SE in this interaction. Supporting Evidence: PMID:34449907 SEAP1 associates with the DCL1 complex, and may promote the interaction of the DCL1 complexes with pri-miRNAs. |
| GO:0005634 nucleus | EXP PMID:19245862 Phosphoproteomic analysis of nuclei-enriched fractions from ... | ACCEPT | Summary: SE was detected as a phosphoprotein in nuclei-enriched fractions. This agrees with imaging studies placing SE in the nucleus. Reason: Nuclear localization is supported by several independent studies (proteomics, GFP imaging, BiFC). SE acts in the nucleoplasm and on chromatin as well as in speckles and dicing bodies, so nucleus is an appropriate general location. Supporting Evidence: PMID:16889646 We further demonstrate that SE is localized in the nucleus PMID:19245862 We identified novel phosphorylation sites on transcription factors, chromatin remodelling proteins, RNA silencing components and the spliceosome. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic nuclear localization. It agrees with the experimental data. Reason: Consistent with experimental nuclear localization of SE. Supporting Evidence: PMID:16889646 We further demonstrate that SE is localized in the nucleus |
| GO:0005634 nucleus | ISS PMID:11402159 The arabidopsis serrate gene encodes a zinc-finger protein r... | ACCEPT | Summary: Nuclear localization inferred by sequence similarity in the cloning paper. Later experiments confirmed it. Reason: Consistent with experimental nuclear localization of SE. Supporting Evidence: PMID:17442570 SE predominantly localizes to nuclear speckles |
| GO:0005730 nucleolus | HDA PMID:15496452 Proteomic analysis of the Arabidopsis nucleolus suggests nov... | KEEP AS NON CORE | Summary: SE was identified in a mass-spectrometry inventory of purified Arabidopsis nucleoli. Imaging studies place SE in the nucleoplasm, speckles and dicing bodies, not specifically in the nucleolus. Reason: This is a high-throughput proteomic detection. The cached text does not let us check the SE-specific evidence, and nucleolar fractions often include nucleoplasmic RNA-processing factors. We keep the curator's annotation but treat it as non-core, because the documented functional locations of SE are the nucleoplasm, nuclear speckles and dicing bodies. Supporting Evidence: PMID:17442570 Unlike DCL1 and HYL1, SE was distributed in a heterogeneous subnuclear pattern in a cell-type dependent manner |
| GO:0005846 nuclear cap binding complex | IPI PMID:24137006 The SERRATE protein is involved in alternative splicing in A... | MODIFY | Summary: SE binds both CBC subunits, CBP80/ABH1 (AT2G13540) and CBP20 (AT5G44200), as shown by BiFC, pull-down and co-IP. Reason: The interaction is well supported. However, the nuclear cap-binding complex is the CBP20/CBP80 cap-binding heterodimer, and SE is an associated partner rather than a subunit, as is ARS2 in the metazoan CBC-ARS2 assembly. The IPI evidence is best captured as the molecular function mRNA cap binding complex binding (GO:0140262). Human SRRT/ARS2 carries the same term by IDA. Proposed replacements: mRNA cap binding complex binding Supporting Evidence: PMID:24137006 using Bimolecular Fluorescence Complementation (BiFC), pull-down and co-immunoprecipitation experiments, we show that both subunits of AtCBC, AtCBP20 and AtCBP80 interact with AtSE. PMID:30152752 SE/ARS2 executes its function in conjunction with the nuclear cap-binding complex (CBC), which consists of two subunits (CBP20 and CBP80) |
| GO:0006355 regulation of DNA-templated transcription | TAS PMID:11402159 The arabidopsis serrate gene encodes a zinc-finger protein r... | MODIFY | Summary: The original TAS came from the cloning paper's speculation that SE acts through chromatin modification. Later ChIP and proteomic work shows that chromatin-bound SE associates with paused and elongating Pol II and promotes Pol II occupancy on more than 1000 mainly intronless genes. Reason: SE does have a transcriptional role, but the evidence supports a more specific term. SE positively regulates Pol II transcription of intronless target genes (PMID:30152752). The 2001 speculation about chromatin modification has not been borne out. This role is non-core compared with miRNA processing. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:30152752 Chromatin-bound SE liaised with paused and elongating polymerase II complexes and promoted their association with intronless target genes. |
| GO:0008380 RNA splicing | IMP PMID:18550839 Dual roles of the nuclear cap-binding complex and SERRATE in... | MODIFY | Summary: se mutants accumulate many partially spliced transcripts, as do cbp20 and cbp80 mutants. These defects are not caused by reduced miRNA processing. Reason: The defects concern Pol II pre-mRNA introns spliced by the spliceosome, so mRNA splicing, via spliceosome is the supported specific term. Tiling-array evidence (abstract only here) shows intron retention shared with CBC mutants and not seen in other miRNA-pathway mutants. This indicates a direct, CBC-linked role. Proposed replacements: mRNA splicing, via spliceosome Supporting Evidence: PMID:18550839 Whole-genome tiling array analyses reveal that se, abh1/cbp80, and cbp20 mutants also share similar splicing defects, leading to the accumulation of many partially spliced transcripts. PMID:18550839 introns retained in se, abh1/cbp80, and cbp20 mutants are not affected by mutations in other genes required for miRNA processing or for nonsense-mediated mRNA decay |
| GO:0010267 ta-siRNA processing | IMP PMID:16889646 SERRATE is a novel nuclear regulator in primary microRNA pro... | KEEP AS NON CORE | Summary: se mutants have less ta-siRNA. ta-siRNA biogenesis is triggered by miRNA-directed cleavage of TAS transcripts (miR173, miR390), so the effect follows from the SE requirement for miRNA production. Reason: The phenotype is real, but the most likely explanation is indirect, through production of the initiating miRNAs. DCL4/DRB4 process ta-siRNA precursors, not DCL1/SE. This matches the DRB1/HYL1 review, which keeps the same row as non-core. Supporting Evidence: PMID:16889646 SE is critical for the accumulation of multiple miRNAs and the trans-acting small interfering RNA (ta-siRNA) |
| GO:0010445 nuclear dicing body | IDA PMID:17442570 Identification of nuclear dicing bodies containing proteins ... | ACCEPT | Summary: Live imaging and BiFC show SE interacting with DCL1 and HYL1 in dicing bodies, although SE is present in D-bodies in only about 20% of nuclei. Later work shows that SE condensates are needed to form D-bodies. Reason: The D-body is where SE carries out its core function in pri-miRNA processing. Its presence there is partial and transient, but it is functionally essential, since SE phase separation drives D-body assembly (PMID:33288888). Supporting Evidence: PMID:17442570 bimolecular fluorescence complementation (BiFC) shows that DCL1, HYL1, and SE interact in D-bodies PMID:33288888 mutation of SE abrogates the formation of D-bodies in vivo, which indicates that D-bodies arise through SE-mediated phase separation |
| GO:0016070 RNA metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: The broad RNA-metabolism term is correct but uninformative. SE acts in pri-miRNA processing and pre-mRNA splicing. Reason: The term is correct but too general. The specific processes supported by experimental evidence, and already carried by SE, are primary miRNA processing and mRNA splicing via the spliceosome. Proposed replacements: primary miRNA processing mRNA splicing, via spliceosome Supporting Evidence: PMID:16977334 We show that SE is a general regulator of miRNA levels affecting the processing of primary miRNA to miRNA. PMID:18550839 se, abh1/cbp80, and cbp20 mutants also share similar splicing defects |
| GO:0016604 nuclear body | IBA GO_REF:0000033 | MODIFY | Summary: The family-level nuclear-body assertion is correct for SE. Arabidopsis SE has experimental localization to two specific kinds of nuclear body, nuclear speckles and nuclear dicing bodies. Reason: The IBA placement is sound. For Arabidopsis SE, however, the two specific nuclear-body subtypes are directly supported and already carried by the gene (nuclear speck by IDA/EXP, nuclear dicing body by IDA), so the general term is refined to both. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000323018 · PTN000323018 SUPPORTS TRANSFER Nuclear-body localization is conserved across the SE/ARS2 node and SE is inside the clade. The MODIFY only sharpens the term to the two nuclear-body subtypes observed for SE. It does not dispute the transfer. Proposed replacements: nuclear speck nuclear dicing body Supporting Evidence: PMID:17442570 SE predominantly localizes to nuclear speckles PMID:17442570 bimolecular fluorescence complementation (BiFC) shows that DCL1, HYL1, and SE interact in D-bodies |
| GO:0016607 nuclear speck | EXP PMID:26227967 The RNA-binding protein HOS5 and serine/arginine-rich protei... | ACCEPT | Summary: SE interacts with HOS5, RS40 and RS41 in nuclear splicing speckles, shown by co-localization of the BiFC signal with the speckle marker CypRS64. Reason: SE is found mainly in nuclear speckles, as shown by several independent imaging studies. Supporting Evidence: PMID:26227967 all of these splicing-related factors directly interact with both HYL1 and SE in nuclear splicing speckles |
| GO:0016607 nuclear speck | IDA PMID:17442570 Identification of nuclear dicing bodies containing proteins ... | ACCEPT | Summary: Live-cell imaging shows that SE is mainly in nuclear speckles, where it self-interacts. Reason: Direct imaging evidence. Supporting Evidence: PMID:17442570 SE predominantly localizes to nuclear speckles |
| GO:0016607 nuclear speck | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping. It agrees with the experimental data. Reason: Consistent with the direct imaging evidence for nuclear speckle localization. Supporting Evidence: PMID:17442570 SE predominantly localizes to nuclear speckles |
| GO:0030674 protein-macromolecule adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: SE/ARS2 proteins act as adaptors that bring effector proteins to cap-bound RNAs and to processing complexes. Arabidopsis SE bridges CPL1 to HYL1, gives CHR2 access to pri-miRNAs, and recruits the NEXT complex. Reason: The IBA placement (seeded by human ARS2 and Drosophila Ars2) is supported by several independent Arabidopsis scaffold and recruitment experiments. Supporting Evidence: PMID:23141542 In the miRNA processing complex, SE functions as a scaffold to mediate CPL1 interaction with HYL1 PMID:32449937 pri-miRNA degradation through the recruitment of the NEXT complex PMID:21685453 SE core provides the platform for HYL1 and DCL1 binding |
| GO:0031047 regulatory ncRNA-mediated gene silencing | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: SE is needed to produce miRNAs, which then guide AGO1-mediated silencing. SE itself does not take part in the silencing step, and it is not needed for sense-transgene PTGS. Reason: In GO, miRNA processing (GO:0035196) is a separate process under regulatory ncRNA processing, not a part of ncRNA-mediated gene silencing. SE contributes to making the guide RNA, not to the silencing step carried out by the AGO1-containing complex. Its role is already captured by primary miRNA processing. The genetic link to silencing is real but indirect. Supporting Evidence: PMID:16889646 but is not required for sense post-transcriptional gene silencing |
| GO:0031053 primary miRNA processing | IBA GO_REF:0000033 | ACCEPT | Summary: Pri-miRNA processing is the conserved core process of the SE/ARS2 family, supported experimentally in plants, flies and mammals. Reason: This is the core process. SE stimulates DCL1 cleavage of pri-miRNA in purified systems and is required in vivo. Supporting Evidence: PMID:30152752 SE and its metazoan ortholog ARSENITE RESISTANCE2 (ARS2) form complexes with DICER proteins and are required for efficient, precise primary-miRNA processing PMID:23921632 found that SE is integral to pri-miRNA processing by DCL1 |
| GO:0031053 primary miRNA processing | IMP PMID:16889646 SERRATE is a novel nuclear regulator in primary microRNA pro... | ACCEPT | Summary: se mutants accumulate less of many miRNAs. Genetic analysis places SE with HYL1 and DCL1 at the pri-miRNA processing step, upstream of HEN1. Reason: Core process, consistent with biochemical reconstitution (PMID:18632569, PMID:23921632). Supporting Evidence: PMID:16889646 we provide evidence that SE and HYL1 probably act with DCL1 in processing pri-miRNAs before HEN1 in miRNA biogenesis |
| GO:0031053 primary miRNA processing | IMP PMID:18550839 Dual roles of the nuclear cap-binding complex and SERRATE in... | ACCEPT | Summary: se mutants, like CBC mutants, have fewer mature miRNAs and more pri-miRNAs. Reason: Core process. Supporting Evidence: PMID:18550839 The processing of Arabidopsis thaliana microRNAs (miRNAs) from longer primary transcripts (pri-miRNAs) requires the activity of several proteins, including DICER-LIKE1 (DCL1), the double-stranded RNA-binding protein HYPONASTIC LEAVES1 (HYL1), and the zinc finger protein SERRATE (SE). |
| GO:0048367 shoot system development | IMP PMID:10607301 The SERRATE locus controls the formation of the early juveni... | KEEP AS NON CORE | Summary: se mutants show changes in vegetative and inflorescence phase length, leaf initiation rate and phyllotaxy. Reason: This is a real mutant phenotype, but a pleiotropic consequence of reduced miRNA regulation of developmental regulators. It is not a direct function of SE. Supporting Evidence: PMID:10607301 Characterization of the serrate mutant (CS3257; Arabidopsis Biological Research Center) revealed defects in both vegetative and inflores-cence phase lengths, the timing of phase transitions, leaf number, the leaf initiation rate, and phyllotaxy. |
| GO:0048509 regulation of meristem development | IMP PMID:16222298 SERRATE coordinates shoot meristem function and leaf axial p... | KEEP AS NON CORE | Summary: SE limits the competence of shoot tissue to respond to KNOX expression and regulates PHB through the miRNA pathway. Both affect meristem activity. Reason: This developmental phenotype is mediated mostly by miR165/166-dependent regulation of HD-ZIP III genes. It is non-core. Supporting Evidence: PMID:16222298 SERRATE acts to coordinately regulate meristem activity and leaf axial patterning |
| GO:2000011 regulation of adaxial/abaxial pattern formation | IMP PMID:16222298 SERRATE coordinates shoot meristem function and leaf axial p... | KEEP AS NON CORE | Summary: se mutants have leaf polarity defects caused by misregulation of PHB, a miR165/166 target. Reason: This is a downstream developmental consequence of the SE role in miRNA biogenesis. It is non-core. Supporting Evidence: PMID:16222298 SERRATE acts in a microRNA (miRNA) gene-silencing pathway to regulate expression of the HD-Zip III gene PHABULOSA (PHB) |
| GO:0170054 ribonuclease activator activity | IDA PMID:18632569 The RNA-binding proteins HYL1 and SE promote accurate in vit... | NEW | Summary: Purified recombinant SE increases the rate and accuracy of DCL1 cleavage of pri- and pre-miRNA substrates. Stimulation depends on SE binding DCL1 through its zinc finger and does not require SE binding to RNA. Reason: SE is a non-catalytic cofactor that binds DCL1 and increases its activity. This matches the definition of ribonuclease activator activity. Two independent reconstitution studies show it, and domain mapping shows that DCL1 stimulation by SE can happen without SE binding RNA. This is SE's own activity on the nuclease, not a necessity phenotype. DCL1 performs the cleavage, and SE's activity is to activate DCL1. The comparator check passes. HYL1/DRB1, the other DCL1 cofactor, is given the same MF in its review and in the plant_mirna_biogenesis module, which already asserts GO:0170054 for SE. The term does not duplicate any existing SE annotation. Supporting Evidence: PMID:18632569 We show that recombinant HYL1 and SE proteins accelerate the rate of DCL1-mediated cleavage of pre- and pri-miR167b substrates and promote accurate processing. PMID:23921632 the interaction with the ZnF domain of SE becomes indispensible and stimulates the activity of DCL1 without requiring SE binding to RNA |
| GO:0140693 molecular condensate scaffold activity | IDA PMID:33288888 Phase separation of SERRATE drives dicing body assembly and ... | NEW | Summary: SE forms droplets in vitro and draws DCL1, HYL1 and pri/pre-miRNAs into them. SE mutation abolishes D-body formation in vivo, and disrupting SE phase separation reduces miRNA processing. Reason: This is an activity of SE itself. SE is the component that drives condensation, and the other microprocessor components are recruited into the SE droplets. Both in vitro reconstitution and in vivo loss-of-function show that SE organizes the D-body condensate, which fits the term definition. The cached source is abstract-only, but the abstract states the key findings explicitly. The term is not an ancestor or descendant of any other SE term. Supporting Evidence: PMID:33288888 SE forms droplets and drives DCL1, HYL1 and pri/pre-miRNAs into the droplets in vitro, and mutation of SE abrogates the formation of D-bodies in vivo PMID:33288888 Disruption of SE phase separation greatly reduces its activity in promoting miRNA processing both in vitro and in vivo. |
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Download this section (compressed HTML)Q: Should the CBC association of SE/ARS2 be captured as part_of the nuclear cap binding complex (GO:0005846, defined as the CBP20/CBP80 heterodimer), or should a separate CBC-ARS2/CBC-SE complex term be used, with SE given mRNA cap binding complex binding (GO:0140262)?
Q: Which MIR loci depend most on SE-driven condensation, compared with direct stimulation of DCL1 by SE, and do the two activities need different SE regions (disordered regions versus the zinc finger)?
Q: Is the transcriptional role of SE at intronless genes a direct effect of recruiting Pol II, or does it follow from SE binding nascent capped RNA together with CBC?
Experiment: Reconstitute DCL1 processing with SE separation-of-function variants (disordered-region deletions that abolish phase separation but keep DCL1 binding, and zinc-finger mutants that keep condensation but lose DCL1 binding), and test rescue of se null embryos.
Hypothesis: DCL1 activation and condensate scaffolding are separable activities of SE, and both contribute to miRNA output in vivo.
Type: In vitro reconstitution and genetic complementation
Experiment: Map SE-dependent splicing events against CBP20/CBP80 binding and SE CLIP sites to find out whether SE affects first-intron 5' splice site selection by binding RNA directly or only through CBC.
Hypothesis: SE controls first-intron 5' splice site choice through CBC-bound transcripts and needs its own RNA-binding surface to do so.
Type: CLIP-seq combined with splicing profiling in se and cbp mutants
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