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Microbial RNA encompasses the diverse set of ribonucleic acid molecules found in bacteria, viruses, and fungi, serving as essential components for genetic expression, protein synthesis, and regulation [1, 2]. In bacteria, the ribosomal RNA (rRNA) within the 30S and 50S subunits is a primary target for over half of all natural product antibiotics, which disrupt translation by binding to highly conserved structural motifs [4, 10]. Viral RNA genomes and non-coding elements, such as internal ribosome entry sites (IRES) and regulatory loops, also serve as critical targets for small molecules and antisense therapies designed to halt viral replication [2, 9]. Beyond its role as a template for protein synthesis, microbial RNA acts as a pathogen-associated molecular pattern (PAMP) that triggers the host's innate immune response through receptors like Toll-like receptors (TLRs) [17]. Therapeutic challenges include the emergence of resistance through rRNA mutations and the potential for off-target effects on human mitochondrial ribosomes, which share structural similarities with their bacterial counterparts [5, 15].
Drugs targeting microbial RNA primarily function by binding to specific structural motifs within ribosomal RNA (rRNA) to inhibit protein synthesis, or by targeting viral RNA structures (such as IRES or pseudoknots) to block replication and translation. Antibiotics like aminoglycosides and tetracyclines bind to the 16S rRNA of the 30S subunit, causing translational misreading or blocking tRNA binding, while macrolides and oxazolidinones bind to the 23S rRNA of the 50S subunit to inhibit peptide bond formation or block the nascent peptide exit tunnel.
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