The target of rapamycin signaling pathway regulates mRNA turnover in the yeast Saccharomyces cerevisiae
The target of rapamycin signaling pathway regulates mRNA turnover in the yeast Saccharomyces cerevisiae
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DOI：
10.1091/mbc.12.11.3428
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发表时间：
2001-11-01
影响因子：
3.3
通讯作者：
Decker, CJ
中科院分区：
文献类型：
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作者：
Albig, AR;Decker, CJ
雷帕霉素(TOR)信号通路的靶点是真核生物中营养物质可利用性调节细胞生长的重要机制。我们提供的证据表明，TOR信号通路控制着酿酒酵母的mRNA周转。在营养限制期间(二次移位)或用雷帕霉素(一种TOR的特异性抑制剂)处理后，多个mRNAs被破坏了稳定性，而其他mRNAs的衰变没有受到影响。我们的发现表明，TOR途径对mRNA衰退的调节可能在控制基因表达以应对营养耗竭方面发挥重要作用。TOR途径的抑制加速了酵母中主要的mRNA衰变机制，即依赖于死烯基化的解帽途径。在失稳的mRNAs中，观察到对雷帕霉素有两种不同的反应。一些mRNAs很快就不稳定了，而另一些则只有在长时间暴露后才会受到影响。我们的数据表明，快速反应的mRNAs是不稳定的，因为它们过早地有短的Poly(A)尾巴，要么是快速去烯化的结果，要么是减少的多腺苷基化的结果。相比之下，反应缓慢的mRNA会因快速解压而变得不稳定。综上所述，TOR通路对mRNA周转的控制是复杂的，因为它专门调节一些mRNAs的衰变，而不是其他mRNAs的衰变，而且它似乎通过多种机制来控制衰变。
The target of rapamycin (TOR) signaling pathway is an important mechanism by which cell growth is regulated by nutrient availability in eukaryotes. We provide evidence that the TOR signaling pathway controls mRNA turnover in Saccharomyces cerevisiae. During nutrient limitation (diauxic shift) or after treatment with rapamycin (a specific inhibitor of TOR), multiple mRNAs were destabilized, whereas the decay of other mRNAs was unaffected. Our findings suggest that the regulation of mRNA decay by the TOR pathway may play a significant role in controlling gene expression in response to nutrient depletion. The inhibition of the TOR pathway accelerated the major mRNA decay mechanism in yeast, the deadenylation-dependent decapping pathway. Of the destabilized mRNAs, two different responses to rapamycin were observed. Some mRNAs were destabilized rapidly, while others were affected only after prolonged exposure.. Our data suggest that the mRNAs that respond rapidly are destabilized because they have short poly(A) tails prematurely either as a result of rapid deadenylation or reduced polyadenylation. In contrast, the mRNAs that respond slowly are destabilized by rapid decapping. In summary, the control of mRNA turnover by the TOR pathway is complex in that it specifically regulates the decay of some mRNAs and not others and that it appears to control decay by multiple mechanisms.