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RSS FeedsIJMS, Vol. 23, Pages 1260: 9-Aminoacridine Inhibits Ribosome Biogenesis by Targeting Both Transcription and Processing of Ribosomal RNA (International Journal of Molecular Sciences)

 
 

23 january 2022 12:18:14

 
IJMS, Vol. 23, Pages 1260: 9-Aminoacridine Inhibits Ribosome Biogenesis by Targeting Both Transcription and Processing of Ribosomal RNA (International Journal of Molecular Sciences)
 


Aminoacridines, used for decades as antiseptic and antiparasitic agents, are prospective candidates for therapeutic repurposing and new drug development. Although the mechanisms behind their biological effects are not fully elucidated, they are most often attributed to the acridines’ ability to intercalate into DNA. Here, we characterized the effects of 9-aminoacridine (9AA) on pre-rRNA metabolism in cultured mammalian cells. Our results demonstrate that 9AA inhibits both transcription of the ribosomal RNA precursors (pre-rRNA) and processing of the already synthesized pre-rRNAs, thereby rapidly abolishing ribosome biogenesis. Using a fluorescent intercalator displacement assay, we further show that 9AA can bind to RNA in vitro, which likely contributes to its ability to inhibit post-transcriptional steps in pre-rRNA maturation. These findings extend the arsenal of small-molecule compounds that can be used to block ribosome biogenesis in mammalian cells and have implications for the pharmacological development of new ribosome biogenesis inhibitors.


 
80 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 23, Pages 1256: Protective Effect of Ethyl Rosmarinate against Ulcerative Colitis in Mice Based on Untargeted Metabolomics (International Journal of Molecular Sciences)
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