Pol5 is an essential nuclear and nucleolar MYBBP1A-family protein required for rRNA production. It binds rDNA promoter fragments in S. pombe, while conserved family evidence identifies Pol5 as a pre-rRNA-binding ribosome-assembly factor that supports processing of both ribosomal subunits and formation of the large-subunit peptide exit tunnel. Despite historical DNA polymerase nomenclature and retention of polymerase-like sequence motifs, Pol5 is functionally unrelated to B-family DNA polymerases.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005730 nucleolus | IBA GO_REF:0000033 | ACCEPT | Summary: Pol5 localizes to the nucleolus where it functions in rRNA transcription and ribosome assembly. Multiple studies confirm nucleolar localization. Reason: Retain the PAINT localization because the target also has an independent HDA nucleolus annotation in current GOA and its conserved role is in ribosome biogenesis. The direct S. pombe paper establishes nuclear localization but does not by itself resolve nucleolar enrichment. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000324922 SUPPORTS TRANSFER Conserved MYBBP1A-family nucleolar biology and target HDA localization support the inherited location; target evidence among PAINT descendants is expected rather than circular. |
| GO:0000182 rDNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Pol5 directly binds to rDNA sequences, particularly rDNA promoter fragments, as demonstrated by experimental evidence. Reason: Direct S. pombe experiments showed binding to rDNA promoter fragments. This establishes rDNA binding even though the downstream effect on rRNA production does not by itself prove direct regulation of Pol I transcription. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000996206 SUPPORTS TRANSFER The target's direct rDNA-binding annotation experimentally grounds the inherited family assertion; its inclusion among node descendants is not circular. Supporting Evidence: PMID:16816948 Pol5p is shown to bind to rDNA promoter fragments. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000002 | REMOVE | Summary: InterPro inferred nucleotide binding from a conserved B-family-polymerase signature, but no nucleotide-binding activity has been demonstrated for Pol5. Reason: Pol5 retains polymerase-like sequence motifs but the family is functionally unrelated to B-family DNA polymerases. Motif detection alone does not establish nucleotide binding; direct evidence instead supports rDNA binding in S. pombe and pre-rRNA binding in the budding-yeast homolog. Supporting Evidence: PMID:31745560 Despite its initial characterization as a B-type DNA polymerase, Pol5 is functionally unrelated to these enzymes |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MODIFY | Summary: While pol5 does bind nucleic acids (DNA and RNA), this is a very general term that lacks specificity about pol5's actual binding activities. Reason: The generic term is true but uninformative. Direct S. pombe evidence supports rDNA binding, while the conserved budding-yeast protein contacts the 5' ETS, ITS2, and 25S rRNA; use the two specific binding terms. Proposed replacements: rDNA binding rRNA binding Supporting Evidence: PMID:16816948 Pol5p is shown to bind to rDNA promoter fragments. PMID:31745560 we identify binding sites for Pol5 in the 5' external transcribed spacer and within domain III of the 25S rRNA sequence |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | MODIFY | Summary: Pol5 does bind DNA, specifically rDNA sequences, but the more specific rDNA binding term is more informative. Reason: Direct evidence confirms DNA binding specifically at rDNA promoter fragments. Replace the generic term with rDNA binding rather than retaining an uninformative parent term. Proposed replacements: rDNA binding Supporting Evidence: PMID:16816948 Pol5p is shown to bind to rDNA promoter fragments. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Pol5 localizes to the nucleus, specifically concentrating in the nucleolus. Nuclear localization is well-established. Reason: Correct and well-supported. Pol5 clearly localizes to the nucleus with concentration in the nucleolus. This is a fundamental aspect of the protein's cellular localization and is supported by multiple experimental studies. Supporting Evidence: PMID:16816948 Pol5p is an essential gene, expressed constitutively throughout both the mitotic and meiotic life cycles, and localises to the nucleus. |
| GO:0005730 nucleolus | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate of the IBA nucleolus annotation above. Pol5 clearly localizes to the nucleolus. Reason: Retain this independent InterPro localization inference because current target-specific HDA data also place Pol5 in the nucleolus and the conserved protein acts in ribosome biogenesis there. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | REMOVE | Summary: InterPro transfers a broad transcription-regulation process from the MYBBP1A-family signature. Pol5 affects rRNA output, but current evidence does not establish that it directly regulates DNA-templated transcription. Reason: Direct S. pombe data show rDNA-fragment binding and altered rRNA production, which do not distinguish a transcriptional mechanism from downstream pre-rRNA processing and assembly defects. Conserved mechanistic evidence instead places Pol5 on pre-rRNA during ribosome biogenesis, without demonstrating direct regulation of DNA-templated transcription. Supporting Evidence: PMID:31745560 depletion of Pol5 affects the processing of pre-rRNAs destined for the both the large and small subunits file:SCHPO/pol5/pol5-deep-research-falcon.md Pol5 is best conceptualized as a **trans-acting ribosome biogenesis factor** that couples rDNA transcription and/or co-transcriptional processing to productive ribosome assembly (strongest mechanistic support from *S. cerevisiae*). |
| GO:0005515 protein binding | IPI PMID:16816948 Pol5p, a novel binding partner to Cdc10p in fission yeast in... | REMOVE | Summary: General protein binding term based on interaction with Cdc10p. While technically correct, this is a very uninformative term. Reason: The Cdc10 interaction is experimentally supported, but the generic protein binding term does not describe Pol5's molecular role and should not be retained as a functional annotation. Supporting Evidence: PMID:16816948 Pol5p was discovered through a 2-hybrid screen, with the direct interaction confirmed by in vitro "pull-down" experiments with bacterially expressed proteins |
| GO:0000182 rDNA binding | IDA PMID:16816948 Pol5p, a novel binding partner to Cdc10p in fission yeast in... | ACCEPT | Summary: Duplicate of the IBA rDNA binding annotation but with stronger experimental evidence (IDA). Direct experimental demonstration of rDNA binding. Reason: Accept the direct binding result. The assay establishes promoter-fragment binding as a molecular activity but does not by itself prove that Pol5 directly controls Pol I catalysis. Supporting Evidence: PMID:16816948 Pol5p is shown to bind to rDNA promoter fragments. |
| GO:0001163 RNA polymerase I transcription regulatory region sequence-specific DNA binding | IDA PMID:16816948 Pol5p, a novel binding partner to Cdc10p in fission yeast in... | ACCEPT | Summary: Direct assays showed Pol5 binding to rDNA promoter fragments, matching this specific DNA-binding term. Reason: Retain the curator's specific molecular-function annotation because the abstract explicitly reports binding to rDNA promoter fragments. Full text is unavailable locally, so the curator's sequence-specific interpretation is not overruled; no direct Pol I process claim is inferred from the binding result. Supporting Evidence: PMID:16816948 Pol5p is shown to bind to rDNA promoter fragments. |
| GO:0005634 nucleus | IDA PMID:16816948 Pol5p, a novel binding partner to Cdc10p in fission yeast in... | ACCEPT | Summary: Duplicate nuclear localization annotation with experimental evidence (IDA). Well-supported. Reason: Direct S. pombe evidence establishes nuclear localization. Retain it without making a stronger claim about a direct transcriptional mechanism. Supporting Evidence: PMID:16816948 Pol5p is an essential gene, expressed constitutively throughout both the mitotic and meiotic life cycles, and localises to the nucleus. |
| GO:0006364 rRNA processing | ISO PMID:31745560 Pol5 is required for recycling of small subunit biogenesis f... | ACCEPT | Summary: Pol5 is required for proper rRNA processing, particularly at A2 and C2 cleavage sites, and for 60S subunit assembly. Reason: The S. cerevisiae ortholog directly contacts pre-rRNA, and its depletion disrupts processing of precursors for both subunits. The close orthology and conserved MYBBP1A-family role support transfer of this core process to S. pombe. Propagation Review Root cause: NO FAILURE CORE Sources checked: SGD:S000000781 SUPPORTS TRANSFER Direct pre-rRNA contacts and processing defects in budding-yeast Pol5 support transfer to the conserved S. pombe ortholog. Supporting Evidence: PMID:31745560 Depletion of Pol5 affects the processing of pre-rRNAs destined for the both the large and small subunits. PMID:31745560 we identify binding sites for Pol5 in the 5' external transcribed spacer and within domain III of the 25S rRNA sequence |
| GO:0042790 nucleolar large rRNA transcription by RNA polymerase I | ISO NOT PMID:31745560 Pol5 is required for recycling of small subunit biogenesis f... | ACCEPT | Summary: This NOT ISO annotation distinguishes Pol5's conserved pre-rRNA assembly role from direct participation in nucleolar Pol I transcription. Reason: Accept the curator's orthology-based NOT assertion. Budding-yeast mechanistic work places Pol5 on pre-ribosomal RNA and finds processing and assembly defects; the older S. pombe paper reports promoter-fragment binding and reduced rRNA output but does not demonstrate direct participation in Pol I transcription. Propagation Review Root cause: NO FAILURE CORE Sources checked: SGD:S000000781 SUPPORTS TRANSFER The conserved assembly-factor mechanism supports transferring the negative distinction from direct Pol I transcription. Supporting Evidence: PMID:31745560 Instead, Pol5, and its homolog in humans MYBBP1a, belong to a family of predicted transcription regulators and both appear to play roles in ribosome biogenesis (34,36,37) |
| GO:0019843 rRNA binding | ISO PMID:31745560 Pol5 is required for recycling of small subunit biogenesis f... | NEW | Summary: Proposed orthology-based annotation for Pol5 binding to pre-rRNA during ribosomal-subunit maturation. Reason: Budding-yeast Pol5 directly contacts the 5' ETS and domain III of 25S rRNA. Conserved MYBBP1A-family membership and the accepted S. pombe rRNA-processing annotation support proposing rRNA binding at ISO strength, without claiming that the same sites have been mapped in S. pombe. Propagation Review Root cause: NO FAILURE CORE Sources checked: SGD:S000000781 SUPPORTS TRANSFER Direct pre-rRNA crosslinking evidence on budding-yeast Pol5 supports transfer of rRNA binding to the S. pombe ortholog. Supporting Evidence: PMID:31745560 we identify binding sites for Pol5 in the 5' external transcribed spacer and within domain III of the 25S rRNA sequence |
| GO:0042273 ribosomal large subunit biogenesis | ISO PMID:31745560 Pol5 is required for recycling of small subunit biogenesis f... | NEW | Summary: Proposed orthology-based annotation for Pol5's conserved role in large-subunit maturation. Reason: Budding-yeast Pol5 promotes stable assembly of proteins around the peptide exit tunnel and is required for downstream 60S maturation. The conserved family relationship supports transfer of this specific large-subunit process at ISO strength to S. pombe. Propagation Review Root cause: NO FAILURE CORE Sources checked: SGD:S000000781 SUPPORTS TRANSFER Direct mechanistic evidence for budding-yeast Pol5 in pre-60S assembly supports the orthology transfer. Supporting Evidence: PMID:31745560 During pre-60S biogenesis, Pol5 associates with domain III, where it facilitates the stable association of ribosomal proteins that form the outer face of the peptide exit tunnel (L19 (eL19), L25 (eL25), L27 (eL27) and others). |
| GO:0042274 ribosomal small subunit biogenesis | ISO PMID:31745560 Pol5 is required for recycling of small subunit biogenesis f... | NEW | Summary: Proposed orthology-based annotation for Pol5's conserved role in small-subunit maturation. Reason: Budding-yeast Pol5 is required for turnover of excised 5' ETS fragments and recycling of associated small-subunit assembly factors. The conserved family relationship supports transfer of this specific small-subunit process at ISO strength to S. pombe. Propagation Review Root cause: NO FAILURE CORE Sources checked: SGD:S000000781 SUPPORTS TRANSFER Direct mechanistic evidence for budding-yeast Pol5 in pre-40S assembly-factor recycling supports the orthology transfer. Supporting Evidence: PMID:31745560 Moreover, our data indicate the requirement for Pol5 for turnover of excised fragments of the 5′ ETS and recycling of associated SSU AFs. |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Third duplicate of nuclear localization annotation, from high-throughput localization study. Reason: Retain the target-specific high-throughput nuclear localization, which corroborates the independent IDA and UniProt localization assertions. |
| GO:0005730 nucleolus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: Third duplicate of nucleolar localization annotation from large-scale localization study. Reason: Retain the target-specific high-throughput nucleolar localization. This is the direct target evidence that corroborates the IBA and IEA nucleolus rows. |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: Cytosolic localization detected in high-throughput study, but pol5 primarily functions in the nucleus/nucleolus. Reason: Retain the observed cytosolic pool as non-core. Its functional significance is unknown, whereas Pol5's conserved pre-ribosome role and direct nuclear localization identify nucleus and nucleolus as the principal sites of action; the HDA result should not be dismissed as artifact without contrary evidence. |
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Download this section (compressed HTML)Q: Does acute S. pombe Pol5 depletion alter nascent Pol I transcription independently of its effects on pre-rRNA processing and precursor stability?
Suggested experts: RNA polymerase I transcription specialists, Ribosome biogenesis researchers
Q: Does S. pombe Pol5 directly contact pre-rRNA at sites homologous to the budding-yeast 5' ETS, ITS2, and 25S domain III sites?
Suggested experts: Nucleolar biology experts, Ribosome assembly researchers
Q: Is S. pombe Pol5 binding to rDNA promoter fragments sequence-specific, and how does its affinity for DNA compare with its affinity for pre-rRNA?
Suggested experts: Structural biologists, DNA-protein interaction specialists
Q: How does the pol5-Cdc10 interaction relate to cell cycle control of ribosome biogenesis?
Suggested experts: Cell cycle researchers, Ribosome biogenesis experts
Q: Does Eso1-dependent acetylation of Pol5 K47 regulate Pol5 recruitment to pre-ribosomes, pre-rRNA binding, or ribosomal-subunit maturation?
Suggested experts: Ribosome biogenesis researchers, Protein acetylation researchers
Experiment: Combine acute Pol5 depletion with metabolic labeling or a Pol I run-on assay and pre-rRNA northern analysis to separate primary transcription defects from processing and precursor-turnover defects
Type: GENOMICS
Experiment: Perform paired Pol5 CRAC or CLIP and ChIP-seq in S. pombe to compare direct pre-rRNA contacts with rDNA occupancy
Type: GENOMICS
Experiment: Test purified S. pombe Pol5 binding to promoter DNA, nonspecific DNA, and pre-rRNA using competition assays to establish substrate preference and sequence specificity
Type: BIOCHEMICAL
Experiment: Profile pre-rRNA intermediates and polysomes after acute Pol5 depletion to test for conserved processing blocks, 60S deficiency, and half-mer formation
Type: BIOCHEMICAL
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