ReIE, a global inhibitor of translation, is activated during nutritional stress
ReIE, a global inhibitor of translation, is activated during nutritional stress
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DOI：
10.1073/pnas.251327898
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发表时间：
2001-12-04
影响因子：
11.1
通讯作者：
Gerdes, K
中科院分区：
文献类型：
--
作者：
Christensen, SK;Mikkelsen, M;Gerdes, K
这种严格的反应被定义为氨基酸饥饿引起的生理变化。其中许多变化依赖于由REIA(ppGpp合成酶I)合成的调节核苷酸ppGpp(鸟苷四磷酸)，RelA编码的蛋白质。大肠杆菌的第二个REL基因座称为relBE，编码RelE细胞毒素和RelB抗毒素。RelB抵消了Rele的毒性作用。此外，RelB还是一种relBE转录的自阻遏子。在这里，我们揭示了一种不依赖于ppGpp的机制，它在氨基酸饥饿期间降低了翻译水平。人工过表达的Rele严重抑制了翻译。在氨基酸饥饿期间，relBE的存在导致饥饿后翻译水平的显著下降。同时，relBE转录被迅速而强烈地诱导。转录的诱导独立于relA和SPOT(编码ppGpp合成酶II)，而依赖于Lon蛋白酶。一直以来，降解RelB都需要LON。用LaCL调控的启动子替换relBE启动子表明，在饥饿期间，维持适当的ReiB：Rele比率需要强大的和持续的relBE转录。因此，relBE可以被认为是一种以前没有特征的应激反应元件，它在营养应激期间降低了整体翻译水平。
The stringent response is defined as the physiological changes elicited by amino acid starvation. Many of these changes depend on the regulatory nucleotide ppGpp (guanosine tetraphosphate) synthesized by ReIA (ppGpp synthetase I), the relA-encoded protein. The second rel locus of Escherichia coli is called relBE and encodes RelE cytotoxin and RelB antitoxin. RelB counteracts the toxic effect of RelE. In addition, RelB is an autorepressor of relBE transcription. Here we reveal a ppGpp-independent mechanism that reduces the level of translation during amino acid starvation. Artificial overexpression of RelE severely inhibited translation. During amino acid starvation, the presence of relBE caused a significant reduction in the poststarvation level of translation. Concomitantly, relBE transcription was rapidly and strongly induced. Induction of transcription occurred independently of relA and spoT (encoding ppGpp synthetase II), but instead depended on Lon protease. Consistently, Lon was required for degradation of RelB. Replacement of the relBE promoter with a Lacl-regulated promoter indicated that strong and ongoing transcription of relBE is required to maintain a proper ReiB:RelE ratio during starvation. Thus relBE may be regarded as a previously uncharacterized type of stress-response element that reduces the global level of translation during nutritional stress.