TBI, Université de Toulouse, CNRS, INRAE, INSA, Toulouse, France.
Nucleic Acids Res. 2023 Apr 11;51(6):2877-2890. doi: 10.1093/nar/gkad104.
mRNA sits at the crossroads of transcription, translation and mRNA degradation. Many questions remain about the coupling of these three processes in Escherichia coli and, in particular, how translation may have an effect on mRNA degradation and transcription. To characterize the interplay between mRNA degradation and translation while accounting for transcription, we altered the translation initiation or elongation and measured the effects on mRNA stability and concentration. Using a mapping method, we analysed mRNA concentration and stability at the local scale all along the transcript. We showed that a decrease in translation initiation efficiency destabilizes the mRNA and leads to a uniform decrease in mRNA concentration throughout the molecule. Prematurely terminating translation elongation by inserting a stop codon is associated with a drop in local mRNA concentration downstream of the stop codon, due to the uncoupling of transcription and translation. In contrast, this translation alteration uniformly destabilizes the coding and ribosome-free regions, in a process triggered by RNase E activity, and its ability to form the RNA degradome. These results demonstrate how ribosomes protect mRNA molecules and highlight how translation, mRNA degradation and transcription are deeply interconnected in the quality control process that avoids unproductive gene expression in cells.
mRNA 处于转录、翻译和 mRNA 降解的交汇点。许多关于大肠杆菌中这三个过程的偶联问题仍然存在，特别是翻译如何影响 mRNA 降解和转录。为了描述翻译起始或延伸的改变如何影响 mRNA 的稳定性和浓度，我们分析了 mRNA 的稳定性和浓度，在转录过程中，我们在局部范围内对 mRNA 浓度和稳定性进行了分析。我们发现，翻译起始效率的降低会使 mRNA 不稳定，并导致整个分子中 mRNA 浓度的均匀下降。通过插入终止密码子来提前终止翻译延伸与翻译延伸终止密码子下游局部 mRNA 浓度的下降有关，这是由于转录和翻译的解偶联。相比之下，这种翻译改变会在核糖核酸酶 E 活性触发的过程中均匀地使编码区和核糖体游离区不稳定，以及其形成 RNA 降解组的能力。这些结果表明了核糖体如何保护 mRNA 分子，并强调了翻译、mRNA 降解和转录在避免细胞中无产物基因表达的质量控制过程中是如何深度相互关联的。
