Sánchez-Sánchez Francisco, Mittnacht Sibylle
Area de Genética, Facultad de Medicina/Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla-La Mancha, Albacete, Spain.
Bioessays. 2008 Oct;30(10):926-8. doi: 10.1002/bies.20825.
The expression of protein-encoding genes is a complex process culminating in the production of mature mRNA and its translation by the ribosomes. The production of a mature mRNA involves an intricate series of processing steps. The majority of eukaryotic protein-encoding genes contain intron sequences that disrupt the protein-encoding frame, and hence have to be removed from immature mRNA prior to translation into protein. The mechanism involved in the selection of correct splice sites is incompletely understood. A considerable body of evidence suggests that the splicing machinery has suboptimal efficiency and fidelity leading to substantial processing inaccuracy. Here we discuss a recently published article that extends observations that cells rely on nonsense-mediated mRNA decay (NMD) to compensate for such suboptimal processing accuracy. Intriguingly these authors provide evidence for a strong selective pressure in favour of premature termination of mRNA translation in the event of intron retention. The analysis presented implies a positive role of NMD in transcript diversification through alternative splicing and suggest that this ancient surveillance mechanism may have co-evolved with intron acquisition born from the need for quality control of splicing patterns.
蛋白质编码基因的表达是一个复杂的过程，最终产生成熟的mRNA并由核糖体进行翻译。成熟mRNA的产生涉及一系列复杂的加工步骤。大多数真核生物蛋白质编码基因包含内含子序列，这些序列会破坏蛋白质编码框架，因此在翻译成蛋白质之前必须从未成熟的mRNA中去除。选择正确剪接位点所涉及的机制尚未完全了解。大量证据表明，剪接机制的效率和保真度欠佳，导致大量加工错误。在此，我们讨论一篇最近发表的文章，该文章扩展了细胞依靠无义介导的mRNA降解（NMD）来补偿这种欠佳加工准确性的观察结果。有趣的是，这些作者提供了证据，表明在发生内含子保留的情况下，存在有利于mRNA翻译过早终止的强大选择压力。所呈现的分析暗示了NMD在通过可变剪接实现转录本多样化方面的积极作用，并表明这种古老的监测机制可能与因剪接模式质量控制需求而产生的内含子获得共同进化。
