SRrp35 Inhibitors

Chemical inhibitors of SRrp35 target various stages of the RNA splicing process, which is central to the protein's function. Pladienolide B, E7107, and Spliceostatin A all interact with the spliceosome, the complex responsible for cutting and rejoining pre-mRNA to form mature messenger RNA. These inhibitors bind to components of the spliceosome such as SF3b complex, leading to altered splicing. By disrupting this complex, these chemicals directly interfere with the splicing of pre-mRNA transcripts, including those necessary for the proper synthesis of SRrp35. This disruption can inhibit the formation of fully functional SRrp35 protein due to improper or incomplete splicing of its mRNA precursors. Tetrocarcin A goes a step further by blocking RNA synthesis, which is a prerequisite for spliceosome assembly. Without RNA synthesis, the assembly of the spliceosome is compromised, leading to a downstream inhibition of SRrp35's maturation and function.

Additionally, other chemicals act upon different stages of mRNA processing and translation, which can inhibit the function of SRrp35. Madrasin, by inhibiting the splicing factor 3B subunit 1, impairs the splicing machinery upon which the maturation of SRrp35 heavily depends. Isoginkgetin, as a bioflavonoid that inhibits splicing, prevents the proper processing of SRrp35 pre-mRNA. Plitidepsin binds to eukaryotic elongation factor eEF1A2, involved in mRNA transport and localization, which is a critical step for the correct function of the SRrp35 protein. Moreover, Silvestrol and Homoharringtonine inhibit translation initiation and elongation, respectively. Silvestrol disrupts the synthesis of SRrp35 by preventing the translation of its mRNA, while Homoharringtonine inhibits the elongation phase of protein synthesis, leading to a reduction in the synthesis and function of SRrp35 protein. Each of these chemicals, by targeting specific pathways and processes, ensures that the production or function of the SRrp35 protein is compromised, resulting in its functional inhibition.