| 2000 |
RRS1 (yeast Rrs1p) is an essential nuclear protein required for ribosome biogenesis; depletion of Rrs1p causes defects in pre-rRNA processing and assembly of ribosomal subunits. The rrs1-1 mutation also greatly reduced transcriptional repression of rRNA and ribosomal protein genes caused by a secretory defect, placing Rrs1 in a signaling pathway coupling secretion to ribosome synthesis. |
Conditional null mutant (GAL1 promoter depletion), cold-sensitive mutant analysis, transcriptional repression assays in S. cerevisiae |
Molecular and cellular biology |
High |
10688653
|
| 2007 |
Yeast assembly factors Rpf2 and Rrs1 form a ribonucleoprotein neighborhood in preribosomes together with ribosomal proteins rpL5, rpL11, and 5S rRNA. Rpf2 and Rrs1 are required for recruiting rpL5, rpL11, and 5S rRNA into nascent 90S preribosomes; in their absence, 27SB pre-rRNA processing is blocked and abortive 66S pre-rRNPs are prematurely released from the nucleolus. |
In vitro binding assays, co-immunoprecipitation, genetic depletion, pre-rRNA processing analysis, subcellular fractionation |
Genes & development |
High |
17938242
|
| 2015 |
Crystal structure of the Rpf2-Rrs1 core complex from Aspergillus nidulans at 1.5 Å reveals that the Brix domain of Rpf2 is completed by Rrs1 to form two anticodon-binding domain-like modules. The Rpf2-Rrs1 heterodimer makes specific contacts with 5S rRNA, RpL5, and the biogenesis factor Rsa4. Two helices in the Rrs1 C-terminal tail occupy a strategic position to block rotation of 25S rRNA and the 5S RNP, explaining why removal of Rpf2-Rrs1 is required for 60S maturation rearrangements. |
X-ray crystallography (1.5 Å), fitting into cryo-EM density, biochemical interaction data |
Nucleic acids research |
High |
26117542
|
| 2015 |
Crystal structure of the Aspergillus nidulans Rpf2-Rrs1 core complex shows the Rrs1 long α-helix joins the C-terminal half of the Rpf2 Brix domain as part of a single structural unit; the proline-rich linker of Rrs1 wraps around Rpf2. Gel shift analysis demonstrated that the Rpf2-Rrs1 complex binds directly to 5S rRNA, and mutagenesis of Rpf2 R236 (equivalent to ScRpf2 R238) significantly impairs this binding. |
X-ray crystallography, gel shift (EMSA), site-directed mutagenesis |
Nucleic acids research |
High |
25855814
|
| 2009 |
Human RRS1 localizes in the nucleolus during interphase and redistributes to the chromosome periphery during mitosis. RNAi-mediated depletion of RRS1 causes abnormal chromosome alignment, spindle disorganization, mitotic delay, loss of centromeric Shugoshin 1 localization, and premature separation of sister chromatids, establishing a role for RRS1 in chromosome congression. |
Immunofluorescence microscopy, RNA interference, flow cytometry |
FEBS letters |
Medium |
19465021
|
| 2009 |
Mammalian Rrs1 localizes both in the nucleolus and in the endoplasmic reticulum of neurons. Its molecular partner 3D3/lyric shares this dual localization. Both Rrs1 and 3D3/lyric are induced by ER stress in neurons, and ER stress occurs as an early presymptomatic event in a Huntington disease knock-in mouse model. |
Subcellular fractionation, immunofluorescence co-localization, ER stress induction assays, HD mouse model analysis |
The Journal of biological chemistry |
Medium |
19433866
|
| 2015 |
The essential function of Rrs1 in 60S ribosomal subunit biogenesis is conserved between S. cerevisiae and S. pombe. Two-hybrid analysis showed that Rrs1 interactions with Rpf2 (Rfp2) and Ebp2 are conserved in both yeasts. |
Temperature-sensitive mutant complementation, yeast two-hybrid |
Yeast (Chichester, England) |
Medium |
26122634
|
| 2019 |
In Trypanosoma brucei, TbRrs1 is an essential component of the 5S RNP complex. It directly interacts with trypanosome-specific proteins P34/P37, 5S rRNA, TbL5, and TbRpf2. RNAi knockdown of TbRrs1 impairs ribosome subunit formation and 25/28S and 5.8S rRNA processing. |
RNA interference, co-immunoprecipitation, direct binding assays |
mSphere |
Medium |
31391282
|
| 2021 |
RRS1 genomic gain drives overexpression of RRS1 in hepatocellular carcinoma. Mechanistically, RRS1 retains RPL11 in the nucleolus, preventing RPL11 from inhibiting MDM2; this potentiates MDM2-mediated ubiquitination and degradation of p53, thereby promoting HCC cell growth. |
Integrative genomic analysis, in vitro and in vivo tumor growth assays, subcellular fractionation, co-immunoprecipitation, ubiquitination assays |
Science advances |
High |
34433556
|
| 2017 |
RRS1 knockdown in colorectal cancer cells causes G2/M cell cycle arrest, reduces expression of CDC25C and CDK1, increases p53 and CDKN1A/p21 protein levels, and suppresses angiogenesis, establishing RRS1 as a regulator of the G2/M checkpoint and p53 pathway. |
RNAi knockdown, flow cytometry, Western blot, in vivo xenograft assays |
Oncotarget |
Medium |
29137316
|
| 2018 |
RRS1 knockdown in breast cancer cells activates p53 and p21, increases ribosome-free RPL11, and co-immunoprecipitation experiments showed that RRS1 knockdown facilitates direct contact between MDM2 and RPL11/RPL5, thereby activating p53 through the RPL11/MDM2 axis. |
RNAi knockdown, Western blot, co-immunoprecipitation, in vivo xenograft assay |
Journal of cellular and molecular medicine |
Medium |
30320499
|
| 2022 |
RRS1 knockdown in breast cancer BT549 cells reduces RPL11 accumulation in the nucleolus, causing RPL11 to migrate to the nucleoplasm where it binds c-Myc, inhibiting c-Myc-mediated transactivation of SNAIL and decreasing invasion and metastasis. This defines an RRS1-RPL11-c-Myc-SNAIL axis. |
Lentiviral shRNA knockdown, co-immunoprecipitation (COIP), dual-luciferase reporter assay, subcellular fractionation |
International journal of oncology |
Medium |
35179222
|
| 2022 |
RRS1 knockdown inhibits neuroblastoma cell proliferation via dephosphorylation of key PI3K/Akt/NF-κB pathway proteins. Co-immunoprecipitation and mass spectrometry identified RRS1 as physically associating with components of the PI3K/Akt and NF-κB pathways. |
RNAi knockdown, co-immunoprecipitation, mass spectrometry, Western blot, RT-qPCR |
Pediatric research |
Medium |
35523884
|
| 2023 |
RRS1 binds to and stabilizes AEG-1 by inhibiting its ubiquitination and proteasomal degradation, which then promotes MDR1-mediated drug efflux. RRS1 also promotes apoptosis resistance through the ERK/Bcl-2/BAX signaling pathway in breast cancer cells. |
Co-immunoprecipitation, ubiquitination assay, Western blot, cell viability assays |
Molecules (Basel, Switzerland) |
Medium |
37049702 49267538
|
| 2024 |
RRS1 directly interacts with GRP78 (co-immunoprecipitation + mass spectrometry). RRS1 inhibits ubiquitin-proteasome-mediated degradation of GRP78, stabilizing it and activating GRP78-mediated PI3K/AKT signaling to promote breast cancer progression. |
Co-immunoprecipitation, mass spectrometry, ubiquitination assay, Western blot, lentiviral knockdown/overexpression |
Molecules (Basel, Switzerland) |
Medium |
38474562
|
| 2026 |
DCAF13 directly binds RRS1 and catalyzes K27-linked polyubiquitination of RRS1, a non-degradative modification that enhances RRS1 protein stability. DCAF13 deficiency disrupts ribosome assembly and protein synthesis in hematopoietic stem cells, and the defects are only partially rescued by p53 ablation, indicating p53-independent mechanisms also operate downstream. |
Conditional knockout mouse model, Co-immunoprecipitation, ubiquitination assays, ribosome assembly profiling, protein synthesis assays |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
High |
41787937
|
| 2025 |
RRS1 silencing in lung cancer cells activates p53, increases lipid ROS, reduces SLC7A11 and GPX4, and increases ACSL4, triggering ferroptosis. This reduces angiogenesis and cisplatin resistance. Silencing p53 reverses these effects, placing RRS1 upstream of p53 in a ferroptosis-regulatory pathway. |
siRNA knockdown, lipid ROS measurement (BODIPY C11), iron quantification, Western blot, apoptosis flow cytometry, p53 rescue experiment |
Tissue & cell |
Medium |
39983385
|
| 2024 |
In the plant Arabidopsis RRS1/RPS4 immune receptor complex, the E3 ligase RARE directly binds and ubiquitinates the integrated WRKY domain of RRS1 to promote proteasomal degradation of RRS1, indirectly destabilizing RPS4 and compromising complex function. Deubiquitinases UBP12/UBP13 counteract this by deubiquitinating RRS1's WRKY domain, maintaining complex homeostasis. |
Proximity labelling, co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, genetic epistasis |
bioRxivpreprint |
Medium |
bio_10.1101_2024.07.01.599856
|
| 2025 |
The plant RPS4 and RRS1 TIR-NLR proteins form an oligomeric complex whose size does not change upon effector provision. Oligomerization requires TIR domain interactions and nucleotide-binding capacity in RPS4. A cysteine in the RPS4 LRR domain contributes to oligomer stabilization. RPS4 TIR NADase activity is required for immune activation but not for oligomerization, consistent with a model where RRS1 TIR domains suppress RPS4 TIR NADase activity until effector recognition causes conformational relief. |
Size-exclusion chromatography, co-immunoprecipitation, mutagenesis of TIR domains and LRR cysteine, NADase activity assays |
bioRxivpreprint |
Medium |
bio_10.1101_2025.04.11.646618
|