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Cellular transcription and translation machinery

Molecular classification
Enzyme, Ribonucleoprotein complex, Transcription factor, RNA polymerase, Ribosome
01

Overview

The cellular transcription and translation machinery encompasses the integrated system of enzymes, proteins, and RNA molecules responsible for converting genetic information from DNA into functional proteins [1][2]. This complex includes RNA polymerases, which catalyze the synthesis of RNA from a DNA template (transcription), and ribosomes, which facilitate the assembly of amino acids into polypeptide chains based on mRNA sequences (translation) [1][2]. In disease states, such as cancer, this machinery is often hijacked or upregulated to support rapid cell proliferation, while many pathogens rely on the host's machinery for their own replication [3][4]. Consequently, components of this system are major targets for therapeutic intervention; for instance, many antibiotics target bacterial ribosomes to inhibit protein synthesis, and certain chemotherapeutics inhibit RNA polymerases to arrest tumor growth [5][6]. However, targeting these fundamental processes in humans poses significant challenges due to the potential for severe systemic toxicity and off-target effects on essential cellular functions [7]. References: [1] Alberts B, et al. Molecular Biology of the Cell. 6th edition. Garland Science; 2014. [2] National Human Genome Research Institute (NHGRI). "Transcription" and "Translation". genome.gov. [3] Ruggero D. "Translational control in cancer development." Nature Reviews Cancer. 2013;13(6):413-425. [4] Walsh D, Mohr I. "Viral strategies to take over the host translation machinery." Nature Reviews Microbiology. 2011;9(12):860-881. [5] Wilson DN. "Ribosome-targeting antibiotics and mechanisms of bacterial resistance." Nature Reviews Microbiology. 2014;12(1):35-48. [6] Villicaña C, et al. "RNA Polymerase II as a Therapeutic Target in Cancer." Cells. 2020;9(11):2473. [7] Hori S, et al. "Safety and toxicity of targeting the protein synthesis machinery." Expert Opinion on Drug Discovery. 2018;13(12):1153-1165.

Other names
Gene expression machineryProtein synthesis machineryTranscription-translation apparatusCentral dogma machinery
02

Mechanism of action

Inhibition of RNA polymerase activity, interference with ribosomal subunit assembly or function, blocking of tRNA binding, and inhibition of peptide bond formation or translocation [5][6].

03

Biological functions

Gene expressionProtein synthesisRNA synthesisCell growthHomeostasis
04

Disease associations

CancerInfectionGenetic disorderNeurodegenerative disease
05

Safety considerations

Systemic toxicityMitochondrial dysfunctionOff-target effects on healthy tissuesNarrow therapeutic indexInhibition of essential housekeeping genes [7]
06

Interacting drugs

Actinomycin D

7 more in the full profile.

07

Biomarkers

mRNA expression levelsRibosome profilingProtein synthesis rateRNA polymerase II phosphorylation state [6]

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