Schneider-Poetsch Tilman, Usui Takeo, Kaida Daisuke, Yoshida Minoru
Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, Wako, Saitama, Japan.
Nat Chem Biol. 2010 Mar;6(3):189-198. doi: 10.1038/nchembio.326.
Following transcription, genomic information begins a long journey toward translation of its nucleotide sequence into the amino acids of a protein. In eukaryotes, synthesized pre-mRNAs become processed to mature mRNAs by 5'-end capping, splicing, 3'-end cleavage and polyadenylation in the nucleus, before being scrutinized for premature stop codons. Each step requires high precision and control to ensure that an intact and readable message is exported to the cytoplasm before finally becoming translated. Two important aspects of these processes are accurately managed by ribonucleoprotein machineries-the spliceosome and the ribosome. Recently, several natural products targeting these macromolecular assemblies have been reported. For the first time in eukaryotes, these molecules allow chemical disruption and dissection of the sophisticated machinery that regulates post-transcriptional events. Beyond their great potential as bioprobes for investigating mRNA regulation and protein synthesis, these compounds also show promise in opening new therapeutic approaches.
转录之后,基因组信息开始了一段漫长的旅程,即将其核苷酸序列翻译成蛋白质的氨基酸序列。在真核生物中,合成的前体mRNA在细胞核中通过5'-端加帽、剪接、3'-端切割和聚腺苷酸化加工成成熟的mRNA,然后再检查是否存在过早的终止密码子。每个步骤都需要高精度和控制,以确保完整且可读的信息在最终被翻译之前输出到细胞质中。这些过程的两个重要方面由核糖核蛋白机制——剪接体和核糖体精确管理。最近,已经报道了几种靶向这些大分子组装体的天然产物。在真核生物中,这些分子首次能够对调节转录后事件的复杂机制进行化学破坏和剖析。除了作为研究mRNA调节和蛋白质合成的生物探针具有巨大潜力外,这些化合物在开辟新的治疗方法方面也显示出前景。