Target intelligence / Profile preview

Human ribosomal RNA (rRNA)

Target
rRNA
Molecular classification
Nucleic acid, Ribonucleic acid, Ribosomal component, Ribozyme
01

Overview

Human ribosomal RNA (rRNA) molecules are the fundamental structural and catalytic components of the ribosome, the cellular machine responsible for protein synthesis (translation). In humans, the ribosome consists of the 40S small subunit, containing 18S rRNA, and the 60S large subunit, containing 5S, 5.8S, and 28S rRNA (NCBI, 2023). The majority of these rRNAs are transcribed as a single 45S precursor by RNA Polymerase I in the nucleolus, where they undergo extensive modification and cleavage (UniProt, 2024). Beyond providing a scaffold for ribosomal proteins, the 28S rRNA acts as a ribozyme, catalyzing peptide bond formation via its peptidyl transferase center (PubMed: 11061420). In many pathological states, particularly cancer, rRNA synthesis is hyperactivated to support the increased demand for protein production required for rapid cell proliferation (Nature Reviews Cancer, 2008). Consequently, targeting the synthesis and processing of human rRNA has emerged as a viable therapeutic strategy. Small molecules like CX-5461 and BMH-21 are designed to selectively inhibit RNA Polymerase I, thereby depleting rRNA levels and inducing nucleolar stress and p53-dependent apoptosis in malignant cells (Cancer Discovery, 2014). Additionally, classic chemotherapeutics such as 5-fluorouracil exert significant toxicity by incorporating into rRNA, which disrupts ribosome biogenesis and function (Molecular Cancer Therapeutics, 2010).

Other names
Ribosomal ribonucleic acid18S rRNA28S rRNA5.8S rRNA5S rRNACytoplasmic ribosomal RNArDNA transcripts
02

Mechanism of action

Inhibition of RNA Polymerase I-mediated transcription of pre-rRNA, incorporation of antimetabolites into the rRNA strand causing processing defects, and site-specific depurination of the sarcin/ricin loop by ribosome-inactivating proteins.

03

Biological functions

Protein synthesisTranslationPeptidyl transferase activityRibosome biogenesisStructural scaffold for ribosomesDecoding of mRNA
04

Disease associations

CancerRibosomopathyViral infectionDiamond-Blackfan anemiaTreacher Collins syndrome
05

Safety considerations

General cytotoxicity due to essential role in all cellsMyelosuppressionGastrointestinal toxicityNucleolar stress response in non-malignant tissuesPotential for systemic ribotoxicity
06

Interacting drugs

CX-5461

7 more in the full profile.

07

Biomarkers

45S pre-rRNA levelsNucleolar size and morphologyAgNOR (Argyrophilic Nucleolar Organizer Region) protein stainingFibrillarin (FBL) expressionPOLR1A expression levels

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