Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA.
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA.
RNA Biol. 2024 Jan;21(1):1-14. doi: 10.1080/15476286.2024.2303558. Epub 2024 Feb 8.
In recent years, advances in biomedicine have revealed an important role for post-transcriptional mechanisms of gene expression regulation in pathologic conditions. In cancer in general and leukaemia specifically, RNA binding proteins have emerged as important regulator of RNA homoeostasis that are often dysregulated in the disease state. Having established the importance of these pathogenetic mechanisms, there have been a number of efforts to target RNA binding proteins using oligonucleotide-based strategies, as well as with small organic molecules. The field is at an exciting inflection point with the convergence of biomedical knowledge, small molecule screening strategies and improved chemical methods for synthesis and construction of sophisticated small molecules. Here, we review the mechanisms of post-transcriptional gene regulation, specifically in leukaemia, current small-molecule based efforts to target RNA binding proteins, and future prospects.
近年来,生物医学的进展揭示了转录后基因表达调控机制在病理条件下的重要作用。在癌症中,特别是在白血病中,RNA 结合蛋白已成为 RNA 动态平衡的重要调节剂,在疾病状态下往往失调。在确定了这些发病机制的重要性之后,人们已经采取了一些措施,利用基于寡核苷酸的策略以及小分子有机化合物来靶向 RNA 结合蛋白。随着生物医学知识、小分子筛选策略以及用于合成和构建复杂小分子的改进化学方法的融合,该领域正处于一个令人兴奋的转折点。在这里,我们综述了转录后基因调控的机制,特别是在白血病中的机制,当前基于小分子的靶向 RNA 结合蛋白的努力,以及未来的前景。