Host cell nuclear transcriptional machinery

The host cell nuclear transcriptional machinery is a sophisticated assembly of enzymes and proteins, centered around RNA polymerase II, that executes the process of transcribing DNA into messenger RNA (Young, 2011, Nature). This machinery includes general transcription factors, the Mediator complex, and various chromatin-remodeling enzymes that collectively coordinate the initiation, elongation, and termination of transcription (Roeder, 2005, FEBS Letters). In the context of pathology, many viruses, such as HIV-1, HBV, and SARS-CoV-2, exploit these host proteins to express viral genes and replicate their genomes (Ott et al., 2011, Cold Spring Harbor Perspectives in Medicine). While specific components of this machinery, such as Cyclin-dependent kinase 9 (CDK9), are explored as therapeutic targets for cancer and viral infections, the fundamental necessity of transcription for all cellular life often results in significant toxicity. Consequently, drugs acting on this system often face challenges regarding their therapeutic window and potential for systemic side effects (Bensaude, 2011, Transcription).

Other names

Host transcriptional apparatusNuclear transcription complexHost transcription machineryRNA polymerase II transcription complex

Inhibition of RNA polymerase II processivity, DNA intercalation, or inhibition of transcriptional kinases such as CDK7 and CDK9 that regulate the transition from transcription initiation to elongation (Wang & Fischer, 2008, Trends in Pharmacological Sciences).