Gene Expression Is Circular: Factors for mRNA Degradation Also Foster mRNA Synthesis

Gene Expression Is Circular: Factors for mRNA Degradation Also Foster mRNA Synthesis
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DOI:
10.1016/j.cell.2013.05.012
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发表时间:
2013-05-23
期刊:
影响因子:
64.5
通讯作者:
Choder, Mordechai
Choder, Mordechai
中科院分区:
生物学1区
文献类型:
--
作者:
Haimovich, Gal;Medina, Daniel A.;Choder, Mordechai

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维持适当的mRNA水平是调控基因表达的一个关键方面。mRNA合成和衰变之间的平衡决定了这些水平。我们证明大多数酵母mrna是通过细胞质50- 30途径(“decaysome”)降解的,正如之前提出的那样。出乎意料的是,在这一主要途径中,这些mrna的水平对扰动是高度稳健的,因为各种衰变组分的缺陷会导致转录下调。此外,这些成分在细胞质和细胞核之间穿梭,以一种依赖于适当mRNA降解的方式。在细胞核中,它们与染色质结合——优先与转录起始位点上游30 bp相似——并直接刺激转录起始和延伸。衰变体在转录中的核作用与其在mRNA衰变中的细胞质作用有关;反过来,联动似乎依赖于其组成部分的适当穿梭。因此,基因表达过程是循环的,迄今为止的第一个阶段和最后一个阶段是相互联系的。
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 50-to-30 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 similar to 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.