Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Cell. 2013 May 23;153(5):1000-11. doi: 10.1016/j.cell.2013.05.012.
Maintaining proper mRNA levels is a key aspect in the regulation of gene expression. The balance between mRNA synthesis and decay determines these levels. We demonstrate that most yeast mRNAs are degraded by the cytoplasmic 5'-to-3' pathway (the "decaysome"), as proposed previously. Unexpectedly, the level of these mRNAs is highly robust to perturbations in this major pathway because defects in various decaysome components lead to transcription downregulation. Moreover, these components shuttle between the cytoplasm and the nucleus, in a manner dependent on proper mRNA degradation. In the nucleus, they associate with chromatin-preferentially ∼30 bp upstream of transcription start-sites-and directly stimulate transcription initiation and elongation. The nuclear role of the decaysome in transcription is linked to its cytoplasmic role in mRNA decay; linkage, in turn, seems to depend on proper shuttling of its components. The gene expression process is therefore circular, whereby the hitherto first and last stages are interconnected.
维持适当的 mRNA 水平是基因表达调控的关键方面。mRNA 合成和降解之间的平衡决定了这些水平。我们证明,正如先前提出的那样,大多数酵母 mRNA 是通过细胞质 5' 到 3' 途径("降解体")降解的。出乎意料的是,由于各种降解体成分的缺陷导致转录下调,这些 mRNA 的水平对这个主要途径的干扰具有高度的稳健性。此外,这些成分以依赖于适当的 mRNA 降解的方式在细胞质和核之间穿梭。在核内,它们与染色质结合,优先位于转录起始位点上游约 30 个碱基处,并直接刺激转录起始和延伸。降解体在转录中的核作用与其在 mRNA 降解中的细胞质作用相关联;这种关联反过来似乎取决于其成分的适当穿梭。因此,基因表达过程是循环的,迄今为止的第一阶段和最后阶段相互关联。