Target intelligence / Profile preview

DNA-templated transcription (GO:0006351)

Target
GO:0006351
Molecular classification
Enzyme, Transcription factor, Nucleic acid binding, Protein complex
01

Overview

DNA-templated transcription is the fundamental biological process where a specific segment of DNA is copied into RNA by the enzyme RNA polymerase. This process is the first step of gene expression and is essential for the survival, growth, and differentiation of all living organisms, as it produces the messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA) required for protein synthesis. Although 'DNA-templated transcription' is a broad Gene Ontology (GO) term rather than a single molecular target, the machinery that executes this process—most notably DNA-directed RNA polymerases and associated transcription factors—serves as a vital target for various therapeutic agents. In oncology, drugs like Actinomycin D and Lurbinectedin disrupt transcription to kill rapidly dividing cancer cells, while in infectious diseases, antibiotics like Rifampicin selectively target bacterial RNA polymerase to treat infections like tuberculosis. However, because transcription is a universal requirement for cellular function, drugs targeting this process often face significant challenges regarding selectivity and can cause severe systemic side effects.

Other names
Transcription, DNA-templatedRNA synthesisDNA-dependent RNA transcriptionGene transcriptionDNA-directed RNA synthesis
02

Mechanism of action

Inhibition of DNA-directed RNA polymerase activity, blockage of transcription initiation by inhibiting the TFIIH complex, DNA intercalation to prevent strand separation, and induction of RNA polymerase II degradation.

03

Biological functions

Gene expressionRNA synthesisCell differentiationCell growthProtein synthesis regulationSignal transduction
04

Disease associations

CancerViral infectionBacterial infectionGenetic disordersInflammation
05

Safety considerations

Systemic toxicity due to inhibition of essential housekeeping genesNarrow therapeutic indexHepatotoxicityMyelosuppressionNon-selective cytotoxicity
06

Interacting drugs

Rifampicin

7 more in the full profile.

07

Biomarkers

mRNA expression levelsRNA polymerase II C-terminal domain (CTD) phosphorylation statusChromatin accessibility (ATAC-seq)Nascent RNA production (Global Run-On sequencing)

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