Rpp25 Inhibitors

Chemical inhibitors of Rpp25 can impede its function in RNA processing pathways by various means. Alsterpaullone, a cyclin-dependent kinase inhibitor, can hinder the phosphorylation that is necessary for the activation of proteins within the RNA processing machinery in which Rpp25 operates. Similarly, roscovitine targets cyclin-dependent kinases to prevent essential phosphorylation processes, therefore likely inhibiting Rpp25's role in RNA maturation. 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) specifically inhibits RNA Polymerase II, which is responsible for the transcription of mRNA precursors that are substrates for Rpp25, leading to a decrease in Rpp25's functional activity due to reduced substrate availability. Flavopiridol, another broad kinase inhibitor, disrupts the phosphorylation of RNA polymerase II and related factors, likely impairing Rpp25's involvement in RNA processing.

Triptolide and α-Amanitin are potent inhibitors of RNA Polymerase II, which directly leads to reduced RNA synthesis and thus a decrease in RNA precursors that require processing by Rpp25. Actinomycin D, by intercalating into DNA, prevents RNA transcription that includes RNA processed by Rpp25, thereby inhibiting the protein's primary function. Distamycin A binds to the DNA minor groove, which can impede transcription factor binding and consequent transcription, reducing the RNA available for Rpp25 processing. Mitoxantrone, through DNA intercalation and Topoisomerase II inhibition, can lead to decreased synthesis of RNA, indirectly inhibiting Rpp25 by limiting its substrate. Cordycepin, an adenosine analog, terminates RNA synthesis upon incorporation, thereby restricting RNA levels and inhibiting Rpp25's RNA processing activities. Homoharringtonine acts by inhibiting protein synthesis at the translation elongation step, which can indirectly inhibit Rpp25 by affecting the efficiency of cellular RNA processing. Finally, tautomycin, as an inhibitor of protein phosphatases PP1 and PP2A, can lead to an altered phosphorylation state of proteins involved in RNA processing, potentially inhibiting the function of Rpp25 within this pathway.