RBM15 inhibitors target RNA-mediated gene regulatory processes, even though they don't directly inhibit RBM15 itself. Actinomycin D and α-Amanitin act by interfering with transcription. The former achieves this by binding to DNA and hindering RNA polymerase movement, while the latter directly inhibits RNA polymerase II. DRB, by inhibiting RNA polymerase II phosphorylation, affects transcription elongation, showcasing the critical role of phosphorylation in the transcription process.
In the realm of RNA splicing, Pladienolide B, Isoginkgetin, Spliceostatin A, Herboxidiene, and Meayamycin B play key roles. They interfere with spliceosome assembly or function, which is crucial for maturation of pre-mRNA to functional mRNA. Specifically, several of these chemicals, like Pladienolide B and Spliceostatin A, target the SF3B spliceosomal complex or its components. DNA topoisomerases, which play a role in solving DNA supercoiling issues during transcription, are inhibited by ICRF-193. This interference can lead to disruptions in transcription. Lastly, CX-5461 and BMH-21 target RNA polymerase I, directly affecting ribosomal RNA synthesis, showcasing their role in regulating the cellular machinery for protein synthesis.
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