TSR4 encodes a cytoplasmic, client-specific ribosomal protein carrier chaperone for Rps2/uS5. Tsr4 binds the eukaryote-specific N-terminal extension of nascent Rps2/uS5, promotes Rps2 expression and solubility, and releases the client before nuclear import and productive pre-40S assembly. Loss of Tsr4 impairs 40S ribosomal small subunit biogenesis, pre-40S export, and 20S pre-rRNA processing at site D to mature 18S rRNA.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030490 maturation of SSU-rRNA | IBA GO_REF:0000033 | ACCEPT | Summary: The IBA is consistent with target-specific IMP evidence that places TSR4 in 20S pre-rRNA processing and with later mechanistic work on Rps2/uS5 delivery into the 40S biogenesis pathway. Reason: SSU-rRNA maturation is a core downstream consequence of the uS5 chaperone role. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000958897 · PANTHER:PTN000958897 SOURCE STALE OR MISSING Cached GOA identifies this exact ancestral node, but no current PTHR47524 PAINT table or PTN record is present in the repository's PAINT snapshot, so the current node assertion cannot be recovered. SGD:S000005382 · TSR4 SUPPORTS TRANSFER The target's own experimental annotation is a valid descendant seed, not circular evidence; direct TSR4 phenotypes support SSU-rRNA maturation. Supporting Evidence: PMID:19806183 We experimentally evaluated >100 candidate yeast genes in a battery of assays, confirming involvement of at least 15 new genes, including previously uncharacterized genes (YDL063C, YIL091C, YOR287C, YOR006C/TSR3, YOL022C/TSR4). file:yeast/TSR4/TSR4-deep-research-falcon.md TSR4 acts within **small (40S) ribosomal subunit biogenesis**, specifically by enabling accumulation and assembly of Rps2/uS5 into pre-40S particles. |
| GO:0005737 cytoplasm | IEA GO_REF:0000002 | ACCEPT | Summary: Cytoplasmic localization is consistent with direct Tsr4 studies. Reason: Tsr4 acts in the cytoplasm on nascent Rps2/uS5 before nuclear import. Supporting Evidence: PMID:31182640 Tsr4 appears to be restricted to the cytoplasm. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Cytosol is the best location for Tsr4 carrier chaperone activity. Reason: Direct and curated sources place Tsr4 in the cytosol/cytoplasm. Supporting Evidence: PMID:31062022 Tsr4 binds co-translationally to the essential, eukaryote-specific N-terminal extension of Rps2, whereas Nap1 interacts with a large, mostly eukaryote-specific binding surface of Rps6. |
| GO:0042254 ribosome biogenesis | IEA GO_REF:0000043 | MODIFY | Summary: Ribosome biogenesis is correct but too broad for Tsr4. Reason: Replace with the more specific ribosomal small subunit biogenesis term. Proposed replacements: ribosomal small subunit biogenesis Supporting Evidence: PMID:31062022 Mutation of the essential Tsr4 and deletion of the non-essential Nap1 both enhance the 40S synthesis defects of the corresponding r-protein mutants. |
| GO:0005829 cytosol | IDA PMID:31062022 Tsr4 and Nap1, two novel members of the ribosomal protein ch... | ACCEPT | Summary: Direct evidence supports cytosolic localization. Reason: Tsr4 binds Rps2/uS5 co-translationally in the cytosol. Supporting Evidence: PMID:31062022 Tsr4 binds co-translationally to the essential, eukaryote-specific N-terminal extension of Rps2, whereas Nap1 interacts with a large, mostly eukaryote-specific binding surface of Rps6. |
| GO:0140597 protein carrier chaperone | IDA PMID:31062022 Tsr4 and Nap1, two novel members of the ribosomal protein ch... | ACCEPT | Summary: Tsr4 is a dedicated Rps2/uS5 carrier chaperone. The abstract frames dedicated ribosomal-protein chaperones as accompanying clients toward assembly, and the full-text-informed 2025 UniProt IDA directly assigns this activity. Reason: Retain the curated experimental annotation. The abstract-only cache is insufficient to overrule the curator's full-text assessment, and this treatment is consistent with NAP1 and the dedicated r-protein-chaperone cohort. Supporting Evidence: PMID:31062022 Dedicated chaperones protect newly synthesized ribosomal proteins (r-proteins) from aggregation and accompany them on their way to assembly into nascent ribosomes. PMID:31062022 Both factors promote the solubility of their r-protein clients in vitro. While Tsr4 is specific for Rps2, Nap1 has several interaction partners including Rps6 and two other r-proteins. file:yeast/TSR4/TSR4-deep-research-falcon.md **Molecular function (best-supported):** Tsr4 binds **nascent Rps2/uS5** co-translationally in the cytoplasm and acts as a **client-specific chaperone** to stabilize Rps2 and support 40S biogenesis (black2019tsr4isa pages 1-3, rossler2019tsr4andnap1 pages 12-13). |
| GO:0042274 ribosomal small subunit biogenesis | IMP PMID:31062022 Tsr4 and Nap1, two novel members of the ribosomal protein ch... | ACCEPT | Summary: Tsr4 perturbation causes 40S biogenesis defects. Reason: Rps2/uS5 chaperoning is directly tied to small subunit assembly. Supporting Evidence: PMID:31062022 Mutation of the essential Tsr4 and deletion of the non-essential Nap1 both enhance the 40S synthesis defects of the corresponding r-protein mutants. |
| GO:0042274 ribosomal small subunit biogenesis | IGI PMID:31062022 Tsr4 and Nap1, two novel members of the ribosomal protein ch... | ACCEPT | Summary: Genetic evidence with RPS2 supports the 40S biogenesis annotation. Reason: The genetic relationship supports Tsr4's role in Rps2-dependent 40S assembly. Supporting Evidence: PMID:31062022 We report the identification of Nap1 and Tsr4 as direct binding partners of Rps6 and Rps2, respectively. |
| GO:0051082 unfolded protein binding | IDA PMID:31062022 Tsr4 and Nap1, two novel members of the ribosomal protein ch... | MODIFY | Summary: GO:0051082 is obsolete. The evidence shows that Tsr4 binds nascent Rps2 and promotes its solubility, supporting protein folding chaperone activity as a client-stabilization facet of its dedicated carrier-chaperone role. Reason: Replace the obsolete term with GO:0044183 to capture the demonstrated anti-aggregation and client-solubilization activity. This replacement is complementary to the separately curated GO:0140597 carrier annotation. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:31062022 Both factors promote the solubility of their r-protein clients in vitro. |
| GO:0042274 ribosomal small subunit biogenesis | IMP PMID:31182640 Tsr4 Is a Cytoplasmic Chaperone for the Ribosomal Protein Rp... | ACCEPT | Summary: Independent evidence supports the same 40S biogenesis role. Reason: Tsr4 perturbation decreases Rps2 and phenocopies Rps2 depletion. Supporting Evidence: PMID:31182640 Tsr4 perturbation resulted in decreased Rps2 levels and phenocopied Rps2 depletion. |
| GO:0051082 unfolded protein binding | IDA PMID:31182640 Tsr4 Is a Cytoplasmic Chaperone for the Ribosomal Protein Rp... | MODIFY | Summary: GO:0051082 is obsolete. This paper identifies Tsr4 as a cytoplasmic chaperone dedicated to Rps2 and shows the client-stabilization biology captured by GO:0044183. Reason: Protein folding chaperone captures the anti-aggregation facet of the evidence and complements the separately curated carrier activity. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:31182640 Here, we report that Tsr4 cotranslationally associates with Rps2. |
| GO:0051082 unfolded protein binding | IPI PMID:31182640 Tsr4 Is a Cytoplasmic Chaperone for the Ribosomal Protein Rp... | MODIFY | Summary: The IPI evidence identifies the specific Tsr4-Rps2 client interaction, but GO:0051082 is obsolete; GO:0044183 captures the client-stabilization facet of this dedicated interaction. Reason: Replace with protein folding chaperone to capture client stabilization, complementary to the separately curated GO:0140597 carrier annotation. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:31182640 Rps2 harbors a eukaryote-specific N-terminal extension that is critical for its interaction with Tsr4. |
| GO:0005737 cytoplasm | IDA PMID:31182640 Tsr4 Is a Cytoplasmic Chaperone for the Ribosomal Protein Rp... | ACCEPT | Summary: Direct microscopy and functional evidence support cytoplasmic localization. Reason: Tsr4 acts before nuclear import and pre-ribosome assembly. Supporting Evidence: PMID:31182640 Despite Rps2 joining nuclear pre-40S particles, Tsr4 appears to be restricted to the cytoplasm. |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: High-throughput cytoplasmic localization is consistent with targeted studies. Reason: The broad cytoplasm term is correct, though cytosol is more precise. Supporting Evidence: PMID:31182640 Tsr4 appears to be restricted to the cytoplasm. |
| GO:0030490 maturation of SSU-rRNA | IMP PMID:19806183 Rational extension of the ribosome biogenesis pathway using ... | ACCEPT | Summary: The original genetic annotation correctly identifies TSR4 in SSU rRNA maturation. Reason: Later work explains the phenotype through defective Rps2/uS5 handling and 40S assembly. Supporting Evidence: PMID:19806183 We associate the new genes with specific aspects of ribosomal subunit maturation, ribosomal particle association, and ribosomal subunit nuclear export, and we identify genes specifically required for the processing of 5S, 7S, 20S, 27S, and 35S rRNAs. |
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Download this section (compressed HTML)Q: What molecular event releases nascent Rps2 from Tsr4, and is a specific importin or assembly factor the immediate acceptor?
Q: Does Tsr4 directly promote a folded Rps2 conformation, or does it principally prevent aggregation until another factor completes folding and import?
Experiment: Reconstitute nascent Rps2-Tsr4 complexes and test candidate importins and pre-40S factors for direct, directional client handoff using kinetic binding and release assays.
Hypothesis: A defined downstream factor triggers Rps2 release and serves as the immediate Rps2 acceptor in the carrier cycle.
Experiment: Compare Rps2 folding and aggregation with and without Tsr4 using limited proteolysis, structural probes, solubility measurements and subsequent import/assembly competence.
Hypothesis: Tsr4 prevents nonproductive aggregation and assists acquisition of an assembly-competent state before a regulated release step transfers Rps2 to the nuclear-import or pre-40S assembly pathway.
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