| Module/Process | Upstream regulators | Mechanism (phosphosites/localization) | Direct Rim15 substrates/targets | Downstream outcomes | Key evidence (brief) | Primary citations with year+DOI URL |
|---|---|---|---|---|---|---|
| Nutrient-sensing hub controlling G0/quiescence entry | PKA; TORC1→Sch9; Pho80–Pho85 | PKA phosphorylates Rim15 at five RRxS sites and inhibits kinase activity; TORC1/Sch9 and Pho80–Pho85 promote cytoplasmic retention via kinase-insert phosphosites including S1061 and T1075; T1075 promotes Bmh2/14-3-3 binding; nutrient limitation/rapamycin/phosphate withdrawal trigger nuclear accumulation; export requires Msn5 (pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000019, pqac-00000021) | Rim15 itself is regulated rather than acting as substrate in this row | Entry into G0/stationary phase, G1 arrest, activation of starvation-responsive transcriptional program (pqac-00000017, pqac-00000023) | Genetics and localization assays showed rim15 mutants fail to mount rapamycin-induced G0 responses; phosphatase-sensitive mobility shifts and GFP localization linked TOR/Sch9 to Rim15 phosphorylation and nuclear exclusion (pqac-00000021, pqac-00000023) | Pedruzzi et al. 2003, https://doi.org/10.1016/S1097-2765(03)00485-4; Swinnen et al. 2006, https://doi.org/10.1186/1747-1028-1-3 |
| Rim15 structural/enzymatic annotation | Nutrient pathways modulate activity but not basic domain architecture | Large 1770-aa AGC/Greatwall-like Ser/Thr kinase with N-terminal PAS domain, central kinase domain with large insert between motifs VII–VIII, C2HC zinc-finger-like region, and non-canonical REC domain; autophosphorylates; catalytic Lys823 required for activity (pqac-00000008, pqac-00000009, pqac-00000011, pqac-00000015) | Igo1/Igo2 are validated direct phospho-targets; broader consensus remains incompletely defined (pqac-00000015) | Provides biochemical basis for central signaling role and regulated substrate phosphorylation during nutrient limitation | Purified wild-type but not kinase-dead Rim15 phosphorylated substrates on protein arrays/in vitro; domain analyses support multidomain signaling/scaffolding functions (pqac-00000008, pqac-00000015) | Cameroni/Loewith 2007 thesis/archive, https://doi.org/10.13097/archive-ouverte/unige:2502 |
| Greatwall–Endosulfine–PP2A-Cdc55 module | Relief of PKA, TORC1-Sch9, and Pho80–Pho85 inhibition activates Rim15 | Upon activation/nuclear function, Rim15 phosphorylates endosulfines Igo1/Igo2; Igo1 Ser64 is validated; phospho-Igo1/2 inhibit PP2A-Cdc55/B55 (pqac-00000024, pqac-00000029, pqac-00000031) | Igo1 Ser64; Igo2 corresponding conserved site (pqac-00000015, pqac-00000024, pqac-00000031) | PP2A-Cdc55 inhibition; preservation of phosphorylated targets such as Gis1/Sic1-related outputs; promotion of quiescence and gametogenesis; contribution to mRNA protection (pqac-00000024, pqac-00000027, pqac-00000028) | Protein microarray + in vitro kinase assays + MS mapped Igo1 Ser64; phospho-Ser64 antibodies and mutational analysis showed Ser64 is necessary for Rim15-dependent G0 traits; genetic studies linked Rim15-Igo1/2 to PP2A-Cdc55 inhibition (pqac-00000024, pqac-00000029, pqac-00000031) | Sarkar et al. 2014, https://doi.org/10.1371/journal.pgen.1004456; Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004 |
| Stress-responsive transcription via Msn2/4 | Upstream inhibition by PKA and TORC1-Sch9 is relieved during starvation | Rim15 enters nucleus and stimulates Msn2/Msn4-dependent STRE genes; Msn2 is directly phosphorylated by Rim15 in vitro, while the precise mechanism for Msn4 remains less direct/fully resolved (pqac-00000026, pqac-00000027, pqac-00000028) | Msn2 direct in vitro substrate; Msn4 functional downstream effector (pqac-00000026, pqac-00000027) | Environmental stress response, antioxidant defense genes, reserve carbohydrate accumulation, quiescence-associated survival (pqac-00000025, pqac-00000027, pqac-00000028) | In vitro kinase assays demonstrated Rim15→Msn2 phosphorylation; classic genetics placed Msn2/4 downstream of Rim15 in G0/stress programs (pqac-00000026, pqac-00000027) | Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004; Pedruzzi et al. 2003, https://doi.org/10.1016/S1097-2765(03)00485-4 |
| Heat-shock/stress transcription via Hsf1 | Rim15 activated when PKA/TORC1 repression is relieved by glucose depletion/starvation | Rim15 directly phosphorylates Hsf1 in vitro; supports induction and stabilization of some Hsf1 target transcripts during glucose depletion (pqac-00000026, pqac-00000030) | Hsf1 (direct in vitro substrate) (pqac-00000026, pqac-00000030) | Heat-shock/stress gene expression, including HSP26-linked responses, contributing to stress resistance (pqac-00000026, pqac-00000028) | Purified Rim15 phosphorylated Hsf1 fragments in vitro; transcript assays showed Rim15-dependent induction/stabilization of Hsf1 targets under glucose depletion (pqac-00000026, pqac-00000030) | Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004 |
| Gis1/PDS transcriptional branch | Activated indirectly downstream of Rim15 and antagonism of PP2A-Cdc55 | Rim15 does not directly phosphorylate Gis1 detectably in vitro; instead phospho-Igo1/2 inhibit PP2A-Cdc55, helping maintain Gis1 in an active phosphorylated state and/or promoter recruitment (pqac-00000026, pqac-00000027, pqac-00000029) | No strong evidence for direct Rim15→Gis1 phosphorylation; indirect regulation via Igo1/2–PP2A-Cdc55 (pqac-00000026, pqac-00000027) | Post-diauxic shift (PDS) gene expression, stationary-phase transcriptional remodeling, oxidative/stress adaptation (pqac-00000025, pqac-00000027) | Genetic epistasis supports Gis1 downstream of Rim15; biochemical work supports the indirect Igo1/2→PP2A-Cdc55 route rather than direct phosphorylation (pqac-00000026, pqac-00000029) | Swinnen et al. 2014, https://doi.org/10.1111/1567-1364.12097; Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004 |
| mRNA stability / decapping control | Rim15 activation under nutrient limitation | Rim15-phosphorylated Igo1/2 antagonize 5′→3′ mRNA decay, in part via association with decapping factor Dhh1; this is downstream of Rim15 kinase action on Igo proteins (pqac-00000026, pqac-00000027, pqac-00000028) | Igo1/Igo2 are direct Rim15 substrates mediating this branch (pqac-00000026, pqac-00000031) | Stabilization/translation of nutrient-regulated mRNAs during starvation/quiescence entry (pqac-00000026, pqac-00000027, pqac-00000028) | Review synthesis and primary data indicate phospho-Igo proteins protect mRNAs from decapping-dependent degradation; IGO1/2 deletion reduces induction of Rim15-responsive genes such as BTN2/HSP26 (pqac-00000026, pqac-00000030) | Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004; Swinnen et al. 2014, https://doi.org/10.1111/1567-1364.12097 |
| Autophagy/gametogenesis-linked survival program | Nutrient starvation activates Rim15 module | Rim15 phosphorylates Igo1/Igo2 to oppose PP2A-Cdc55; Igo1/2 are required for pre-meiotic autophagy, though autophagy defect alone does not fully explain sporulation defect (pqac-00000024) | Igo1/Igo2 (direct); downstream autophagy effectors not fully resolved here (pqac-00000024) | Entry into gametogenesis and starvation survival; quiescence and sporulation via distinct downstream mechanisms (pqac-00000024) | Genetic deletion of IGO1/2 impaired pre-meiotic autophagy and sporulation; authors concluded the Rim15-Endosulfine-PP2A-Cdc55 module governs quiescence and gametogenesis through distinct mechanisms (pqac-00000024) | Sarkar et al. 2014, https://doi.org/10.1371/journal.pgen.1004456 |
| Quiescence phosphoproteome and recent 2023 systems-level updates | Starvation signal context (carbon vs phosphorus vs nitrogen) intersects with Rim15 dependence | Temporal SILAC proteomics/phosphoproteomics in WT vs rim15Δ during starvation identified 1,277 proteins and 1,472 phosphorylation events; 11 common phosphorylation targets increased in WT vs rim15Δ; IGO1 S64 detected before starvation as Rim15-dependent (pqac-00000032, pqac-00000033, pqac-00000034, pqac-00000036) | Confirmed/implicated: IGO1 S64 plus candidate broader targets enriched in RNA metabolism, translation, proteostasis, glycogen metabolism (pqac-00000032, pqac-00000034) | Rim15 contributes to quiescence survival especially under phosphorus and nitrogen starvation; regulates mitochondrial/proteostasis and RNA/translation functions (pqac-00000032, pqac-00000035) | Quantitative study found 298 proteins (carbon) and 82 proteins (phosphorus) with genotype-dependent dynamics; survival defects were stronger in phosphorus/nitrogen starvation than carbon starvation (pqac-00000032, pqac-00000035) | Sun et al. 2023 preprint, https://doi.org/10.1101/2023.08.03.551843 |
| Fermentation control / industrial implementation | TORC1–Rim15–PP2A-B55 axis; natural/engineered RIM15 loss-of-function | Natural sake-yeast frameshift rim15^5055insA truncates Rim15; RIM15 loss increases fermentation rate, while restoring functional RIM15 improves stress tolerance and some brewing traits; CDC55/PP2A-B55 mediates much of the effect downstream (pqac-00000037, pqac-00000041, pqac-00000044) | Rim15 pathway outputs involve Igo1/2 and PP2A-B55/Cdc55; direct fermentation substrate not defined (pqac-00000041, pqac-00000044) | Faster alcoholic fermentation, higher early CO2 evolution and ethanol production, but trade-offs in quiescence entry/stress tolerance/cell survival (pqac-00000037, pqac-00000043, pqac-00000044) | In laboratory strains, rim15 mutants showed higher peak CO2 emission (e.g., 180.8 ± 11.5 vs 235.3 ± 18.1 ml/6 h) and higher ethanol after 20 days (17.03% ± 0.44% v/v); restoring ScRIM15 in K701 improved stress tolerance and reduced cell death in high-ethanol mash (pqac-00000043, pqac-00000044, pqac-00000045) | Watanabe et al. 2012, https://doi.org/10.1128/AEM.00165-12; Watanabe et al. 2019, https://doi.org/10.1128/AEM.02083-18 |


*Table: This table summarizes validated functional annotation for Saccharomyces cerevisiae Rim15 (UniProt P43565), including upstream regulation, localization and phosphosite mechanisms, direct substrates, downstream biological roles, and key primary literature supporting each module.*