Sm Inhibitors

Chemical inhibitors of Sm proteins disrupt various cellular processes that are essential for the proper function of these proteins in RNA splicing. Amiloride can alter intracellular pH by inhibiting the Na+/H+ exchange process, which is crucial for maintaining the environment necessary for Sm proteins to assemble into spliceosomal snRNPs. Similarly, monensin, as an ionophore, disrupts Na+ gradients, which are essential for maintaining ionic conditions that facilitate the biogenesis and function of Sm protein-containing complexes. Chloroquine raises the pH within acidic vesicles, which can interfere with the intracellular trafficking of snRNPs, essential for the function of Sm proteins in the nucleus. Camptothecin and mitoxantrone, both DNA-damaging agents, can indirectly affect Sm proteins by inhibiting topoisomerase enzymes, thereby leading to transcriptional disturbances that are a prerequisite for the proper assembly of snRNP particles.

Moreover, actinomycin D binds DNA and prevents RNA polymerase from transcribing new RNA, which includes the RNA components necessary for snRNP assembly and, consequently, Sm protein function. Rifampicin, though primarily targeting bacterial RNA polymerase, can also cause a decrease in RNA synthesis in eukaryotic cells, leading to a reduction in the available snRNA for Sm protein binding. Puromycin disrupts protein synthesis, which can reduce the levels of proteins required for snRNP assembly, including Sm proteins. Triptolide's inhibition of transcription can lead to diminished snRNA levels, affecting Sm protein function in snRNPs. Leptomycin B targets the export of RNA/protein complexes from the nucleus, potentially disrupting the Sm protein recycling process. Brefeldin A disrupts the Golgi apparatus, which can indirectly affect Sm proteins by altering the trafficking and modification pathways necessary for their function. Lastly, oxaliplatin forms DNA adducts that can affect transcription, indirectly influencing Sm protein function by impacting the RNA components of snRNPs.