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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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RRS1
regulator of ribosome synthesis 1
Chromosome 8 · 8q13.1
NCBI Gene: 23212Ensembl: ENSG00000179041.4HGNC: HGNC:17083UniProt: Q15050
138PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingprotein binding5S rRNA bindingribosomal large subunit assemblyneurodegenerative diseasepost term pregnancypremature birthbreast cancer
✦AI Summary

RRS1 (regulator of ribosome synthesis 1) is a nuclear protein essential for ribosomal large subunit assembly and 5S ribonucleoprotein particle maturation 1. In eukaryotes, RRS1 functions as a specialized chaperone that guides 5S RNA incorporation into preribosomes through interactions with ribosomal proteins Rpl5 and Rpl11, and coordinates the initial assembly conformations required for large subunit biogenesis 1. RRS1 plays critical roles in multiple cellular processes beyond ribosome assembly. In normal trophoblasts, RRS1 regulates cell proliferation, migration, and invasion; its deficiency impairs trophoblast function and is associated with early pregnancy loss 2. RRS1 also regulates nucleolar assembly and p53 homeostasis through the 5S RNP complex 1. Clinically, RRS1 is significantly overexpressed in breast cancer, hepatocellular carcinoma, and other malignancies, correlating with poor prognosis and lymph node metastasis 34. RRS1 knockdown suppresses cancer cell proliferation and induces apoptosis across multiple cancer types 56. Mechanistically, RRS1 promotes cancer progression through multiple pathways: stabilizing GRP78 to activate PI3K/AKT signaling 7, modulating the AEG-1/AKT/c-Myc axis 4, and regulating the RPL11-c-Myc-SNAIL pathway 8. RRS1 inhibition in vivo reduces tumor growth and metastasis 34, suggesting therapeutic potential.

Sources cited
1
RRS1 forms a complex with Rpf2 that chaperones 5S RNA assembly, localizes the 5S RNP to the nucleolus, and guides its incorporation into preribosomes
PMID: 26159998
2
RRS1 is highly expressed in trophoblasts and regulates their proliferation, migration, and invasion; its deficiency is associated with early pregnancy loss
PMID: 41162766
3
RRS1 is highly expressed in breast cancer cell line BT549; its knockdown significantly reduces cell viability and induces apoptosis
PMID: 30509086
4
RRS1 knockdown in hepatocellular carcinoma cells suppresses proliferation, inhibits colony formation, increases apoptosis, and arrests cells in G1 phase
PMID: 28849112
5
RRS1 is overexpressed in breast cancer tissues and correlates with poor survival and lymph node metastasis; its knockdown activates p53 through RPL11/MDM2-mediated mechanisms
PMID: 30320499
6
RRS1 knockdown reduces ribosomal protein L11 accumulation in the nucleolus, allowing its nucleoplasmic migration to bind c-Myc, which inhibits SNAIL transactivation and decreases breast cancer invasion
PMID: 35179222
7
RRS1 is overexpressed in breast cancer and linked to lymph node metastasis; it promotes metastasis through the AEG-1/AKT/c-Myc signaling pathway
PMID: 39267538
8
RRS1 stabilizes GRP78 protein through the ubiquitin-proteasome pathway and promotes breast cancer progression via the GRP78-mediated PI3K/AKT signaling pathway
PMID: 38474562
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.47Moderate
post term pregnancyOpen Targets
0.32Weak
premature birthOpen Targets
0.16Weak
breast cancerOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
cancerOpen Targets
0.09Suggestive
cervical cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
retinoblastomaOpen Targets
0.07Suggestive
attention deficit hyperactivity disorderOpen Targets
0.07Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.06Suggestive
papillary thyroid carcinomaOpen Targets
0.05Suggestive
attention deficit-hyperactivity disorder 8Open Targets
0.05Suggestive
intellectual disability, autosomal recessive 59Open Targets
0.05Suggestive
schizophrenia 15Open Targets
0.05Suggestive
Tourette syndromeOpen Targets
0.05Suggestive
autismOpen Targets
0.05Suggestive
Phelan-McDermid syndromeOpen Targets
0.04Suggestive
obesityOpen Targets
0.04Suggestive
type 2 diabetes mellitusOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TSR1Protein interaction100%BYSLProtein interaction100%IMP4Protein interaction99%MDN1Protein interaction99%WDR43Protein interaction98%BMS1Protein interaction97%
Tissue Expression6 tissues
Ovary
100%
Brain
69%
Lung
68%
Liver
62%
Heart
52%
Bone Marrow
26%
Gene Interaction Network
Click a node to explore
RRS1TSR1BYSLIMP4MDN1WDR43BMS1
PROTEIN STRUCTURE
Preparing viewer…
PDB8FKV · 2.47 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.71LoF Tolerant
pLIⓘ
0.19Tolerant
Observed/Expected LoF0.43 [0.27–0.71]
RankingsWhere RRS1 stands among ~20K protein-coding genes
  • #3,351of 20,598
    Most Researched138 · top quartile
  • #5,473of 17,882
    Most Constrained (LOEUF)0.71
Genes detectedRRS1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Effect of RRS1 gene knockdown on BT549 cell line proliferation and apoptosis in breast cancer.
PMID: 30509086
Neoplasma · 2019
1.00
2
RRS1 regulates proliferation, migration, and invasion of HTR-8/SVneo human trophoblasts.
PMID: 41162766
Front Med · 2025
0.90
3
Chaperoning 5S RNA assembly.
PMID: 26159998
Genes Dev · 2015
0.80
4
Knockdown of RRS1 by lentiviral-mediated RNAi promotes apoptosis and suppresses proliferation of human hepatocellular carcinoma cells.
PMID: 28849112
Oncol Rep · 2017
0.70
5
Downregulated RRS1 inhibits invasion and metastasis of BT549 through RPL11‑c‑Myc‑SNAIL axis.
PMID: 35179222
Int J Oncol · 2022
0.60