Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19102, USA.
Sci Adv. 2017 Oct 20;3(10):e1701484. doi: 10.1126/sciadv.1701484. eCollection 2017 Oct.
Accurate transcription is required for the faithful expression of genetic information. To understand the molecular mechanisms that control the fidelity of transcription, we used novel sequencing technology to provide the first comprehensive analysis of the fidelity of transcription in eukaryotic cells. Our results demonstrate that transcription errors can occur in any gene, at any location, and affect every aspect of protein structure and function. In addition, we show that multiple proteins safeguard the fidelity of transcription and provide evidence suggesting that errors that evade these layers of RNA quality control profoundly affect the physiology of living cells. Together, these observations demonstrate that there is an inherent limit to the faithful expression of the genome and suggest that the impact of mutagenesis on cellular health and fitness is substantially greater than currently appreciated.
准确的转录对于忠实表达遗传信息至关重要。为了了解控制转录保真度的分子机制，我们使用新型测序技术首次全面分析了真核细胞中的转录保真度。我们的研究结果表明，转录错误可能发生在任何基因的任何位置，并影响蛋白质结构和功能的各个方面。此外，我们还表明，多种蛋白质可以保护转录的保真度，并提供证据表明，逃避这些 RNA 质量控制层的错误会严重影响活细胞的生理机能。总之，这些观察结果表明，基因组的忠实表达存在内在限制，并表明突变对细胞健康和适应性的影响比目前所认识的要大得多。
