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核糖核酸酶II调节核糖核酸酶PH,并且在饥饿和稳定期对细胞存活至关重要。

RNase II regulates RNase PH and is essential for cell survival during starvation and stationary phase.

作者信息

Sulthana Shaheen, Quesada Ernesto, Deutscher Murray P

机构信息

Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA.

出版信息

RNA. 2017 Sep;23(9):1456-1464. doi: 10.1261/rna.060558.116. Epub 2017 Jun 16.

Abstract

RNase II is the most active exoribonuclease in cell extracts. Yet, its removal appears to have no deleterious effect on growing cells. Here, we show that RNase II is required for cell survival during prolonged stationary phase and upon starvation. The absence of RNase II leads to greatly increased rRNA degradation and to the accumulation of rRNA fragments, both of which lead to a decline in cell survival. The deleterious effects of RNase II removal can be completely reversed by the simultaneous absence of a second exoribonuclease, RNase PH, an enzyme known to be required to initiate ribosome degradation in starving cells. We have now found that the role of RNase II in this process is to regulate the amount of RNase PH present in starving cells, and it does so at the level of RNase PH stability. RNase PH normally decreases as much as 90% during starvation because the protein is unstable under these conditions; however, in the absence of RNase II the amount of RNase PH remains relatively unchanged. Based on these observations, we propose that in the presence of RNase II, nutrient deprivation leads to a dramatic reduction in the amount of RNase PH, thereby limiting the extent of rRNA degradation and ensuring cell survival during this stress. In the absence of RNase II, RNase PH levels remain high, leading to excessive ribosome loss and ultimately to cell death. These findings provide another example of RNase regulation in response to environmental stress.

摘要

核糖核酸酶II是细胞提取物中活性最高的外切核糖核酸酶。然而,去除它似乎对生长中的细胞没有有害影响。在这里,我们表明核糖核酸酶II在延长的稳定期和饥饿时细胞存活中是必需的。核糖核酸酶II的缺失导致rRNA降解大幅增加和rRNA片段积累,这两者都会导致细胞存活率下降。同时缺失第二种外切核糖核酸酶核糖核酸酶PH可以完全逆转去除核糖核酸酶II的有害影响,核糖核酸酶PH是一种已知在饥饿细胞中启动核糖体降解所必需的酶。我们现在发现核糖核酸酶II在这个过程中的作用是调节饥饿细胞中核糖核酸酶PH的量,并且它是在核糖核酸酶PH稳定性水平上这样做的。在饥饿期间,核糖核酸酶PH通常会减少多达90%,因为这种蛋白质在这些条件下不稳定;然而,在没有核糖核酸酶II的情况下,核糖核酸酶PH的量相对保持不变。基于这些观察结果,我们提出在有核糖核酸酶II的情况下,营养剥夺会导致核糖核酸酶PH的量急剧减少,从而限制rRNA降解的程度并确保细胞在这种应激下存活。在没有核糖核酸酶II的情况下,核糖核酸酶PH水平仍然很高,导致核糖体过度损失并最终导致细胞死亡。这些发现提供了核糖核酸酶响应环境应激调节的另一个例子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/088a/5558914/eef7f3b6e83e/1456f01.jpg

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