Target intelligence / Profile preview

Regulatory RNA III (RNAIII) (RNAIII)

Target
RNAIII
Molecular classification
Regulatory RNA, Dual-function RNA, Quorum-sensing effector, Non-coding RNA
01

Overview

Regulatory RNA III (RNAIII) is the primary effector molecule of the accessory gene regulator (agr) quorum-sensing system in Staphylococcus aureus (PubMed: 21957601; PubMed: 11609781). It is a complex, 514-nucleotide dual-function RNA that serves both as a transcript for the delta-hemolysin (hld) peptide and as a trans-acting regulatory RNA (PubMed: 17540507). RNAIII coordinates the switch between the early colonization phase, characterized by the expression of surface adhesins, and the later invasive phase, characterized by the secretion of toxins and proteases (PubMed: 27550441). By base-pairing with target mRNAs, RNAIII represses the translation of surface proteins such as Protein A (spa) and staphylocoagulase (coa) while activating the translation of exotoxins like alpha-hemolysin (hla) (PLOS Pathogens: e1000809). As a central regulator of MRSA pathogenesis, RNAIII is a prominent target for anti-virulence therapies that aim to attenuate bacterial infection without exerting the high selective pressure typical of traditional antibiotics (Frontiers in Microbiology: 9:18). Therapeutic strategies under development include the RNAIII-inhibiting peptide (RIP) and its derivatives, which disrupt the signaling required for RNAIII synthesis, thereby preventing biofilm formation and toxin production in clinical isolates (PubMed: 11609781; Antimicrob Agents Chemother: 52(6):2205-11).

Other names
Staphylococcus aureus RNAIIIagr effector RNAhld transcriptAccessory gene regulator effector RNAIIIDelta-hemolysin transcript
02

Mechanism of action

Inhibition of the quorum-sensing-mediated synthesis of RNAIII or blocking its antisense interaction with target mRNAs to suppress bacterial virulence and biofilm formation.

03

Biological functions

Quorum sensingVirulence factor regulationInhibition of surface protein synthesisActivation of secreted toxin synthesisToxin productionTranslation regulation
04

Disease associations

InfectionStaphylococcus aureus infectionSepsisBiofilm-associated infectionMethicillin-resistant Staphylococcus aureus (MRSA) infectionSkin and soft tissue infection
05

Safety considerations

Rapid renal clearance of peptide-based inhibitorsShort in vivo half-lifeHigh dosage requirements for therapeutic efficacyPotential for drug resistance development
06

Interacting drugs

RNAIII-inhibiting peptide (RIP)

2 more in the full profile.

07

Biomarkers

RNAIII transcript levelsDelta-hemolysin (Hld) productionAgr system activityAlpha-hemolysin (Hla) expression

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