Previous work has shown that thiophosphate, a phosphate analogue, leads to a global shift in the distribution of cellular proteins in a variety of organisms. Thiophosphate, when added to culture media, gets incorporated into the nucleic acids of cells resulting in nuclease-resistant phosphorothioate linkages. Using Escherichia coli, as a model organism, it was found that the global changes in protein expression induced with thiophosphate could be accounted for by significant changes in the absolute transcription levels of more than 1500 genes detected via RNA seq analysis. In fact, 58% of transcripts detected in RNA seq studies using total RNA were increased an average of 44 × fold while the remaining 42% were decreased an average of 20 × fold in thiophosphate-treated cells. Furthermore, microarray results showed no correlation between the transcriptional changes observed and the known stability of the corresponding mRNAs measured. Overall, the total amount of non-ribosomal RNA accumulated in TP-treated cells was increased relative to rRNA ~ 4 × fold (1.5-6 ×). The results further indicated that metabolic changes may play a role in inducing the transcriptional profiles observed with thiophosphate. Indeed, pathway analysis of transcripts showed an increase in routes for phosphoribosyl pyrophosphate (PRPP) synthesis and related derivatives, presumably due to a reduction in RNA turnover. These results raise the possibility that the energy savings with reduced RNA turnover could lead to an increased energy charge in the cell that induces transcriptional changes leading to an increase in biosynthetic processes.

中文翻译：

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磷酸盐类似物诱导的转录本的整体变化：对基因调控的影响。

先前的研究表明，磷酸酯类似物硫代磷酸酯可导致细胞蛋白质在各种生物体中的分布发生全球性变化。当添加到培养基中时，硫代磷酸盐被掺入细胞的核酸中，产生抗核酸酶的硫代磷酸酯键。使用大肠埃希氏菌作为模型生物，发现由硫代磷酸酯诱导的蛋白质表达的整体变化可能是通过RNA seq分析检测到的超过1500个基因的绝对转录水平的显着变化造成的。事实上，在使用总RNA的RNA seq研究中检测到的转录本的58％在硫代磷酸盐处理的细胞中平均增加了44倍，而其余42％的平均减少了20倍。此外，基因芯片结果显示，观察到的转录变化与相应mRNA的已知稳定性之间没有相关性。总体而言，TP处理细胞中积累的非核糖体RNA总量相对于rRNA约增加了4倍（1.5-6倍）。结果进一步表明，代谢变化可能在诱导硫代磷酸酯观察到的转录谱中起作用。实际上，转录本的途径分析表明，磷酸核糖焦磷酸（PRPP）合成和相关衍生物的途径有所增加，这可能是由于RNA转换的减少。这些结果增加了可能性，即通过减少RNA周转而节省的能量会导致细胞中的能量电荷增加，从而诱导转录变化，从而导致生物合成过程的增加。