Target intelligence / Profile preview

RNA biosynthesis

Molecular classification
Enzyme
01

Overview

RNA biosynthesis, primarily known as transcription, is the fundamental biological process by which genetic information from a DNA template is copied into various forms of RNA, including messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA) [9, 13]. This process is executed by RNA polymerase enzymes, which include DNA-directed RNA polymerases (RNAPs) in cellular organisms and RNA-dependent RNA polymerases (RdRp) in many viruses [1, 9, 15]. As it is essential for cell survival, growth, and viral replication, RNA biosynthesis serves as a major therapeutic target for diverse pharmacological agents [10, 18]. For example, antibiotics like rifampicin selectively inhibit bacterial RNA polymerase to treat tuberculosis, while antiviral drugs such as remdesivir and molnupiravir inhibit viral replication by acting as chain terminators or inducing lethal mutations in the viral genome [9, 12, 15]. In oncology, selective inhibitors of RNA polymerase I, such as CX-5461, are being investigated to halt the hyperactive ribosome biogenesis required for rapid tumor cell proliferation [16, 18]. However, therapeutic intervention in this pathway requires high specificity to avoid severe toxicity resulting from the off-target inhibition of essential human cellular or mitochondrial RNA polymerases [12, 13, 15].

Other names
TranscriptionRNA synthesisRNA productionTranscriptional machineryDe novo RNA synthesis
02

Mechanism of action

Inhibition of RNA polymerase activity (either DNA-directed or RNA-dependent), DNA intercalation to prevent transcriptional elongation, or the incorporation of nucleoside analogs into nascent RNA chains resulting in premature chain termination or lethal mutagenesis.

03

Biological functions

TranscriptionGene expressionCell proliferationViral replicationProtein synthesisCell cycle regulation
04

Disease associations

InfectionCancerInflammationGenetic disorder
05

Safety considerations

Systemic cytotoxicity due to non-selective transcription inhibitionMitochondrial toxicity via inhibition of mitochondrial RNA polymerase (POLRMT)Off-target effects on essential host cell RNA polymerasesPotential mutagenicity or teratogenicity of nucleoside analogs
06

Interacting drugs

Rifampicin

6 more in the full profile.

07

Biomarkers

Viral RNA loadPre-ribosomal RNA (pre-rRNA) levelsGlobal transcription rates (e.g., EU/FU labeling)RNA polymerase II promoter occupancy

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