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Alterations of transcription and translation in HeLa cells exposed to amino acid analogs.

机译:暴露于氨基酸类似物的HeLa细胞中转录和翻译的变化。

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Amino acid analogs, like other effectors of the stress response, induce in mammalian cells the same gene products that are induced upon heat shock; incorporation of the analog into protein is required for induction. We show here that induction by analogs involves controls operating at the levels of both transcription and translation. The electrophoretic patterns of newly made mRNAs simplify with time such that the putative stress protein mRNAs are the only species transported from the nucleus. Concomitantly, the patterns of protein synthesis simplify such that the stress proteins become nearly exclusive polypeptide products. Although the normal mRNAs are either not used or used with greatly reduced efficiency, they are not degraded and retain translatability when transferred to cell-free systems. Soon after the stress response has been induced, there follows a defect in the initiation of polypeptide chains, as evidenced by examination of polysome profiles. Upon prolonged exposure, polysomes are recovered, and although they give rise to stress proteins almost exclusively, the normal mRNAs are still present in these structures. Thus, in addition to the initiation defect, a lesion in elongation may also be involved. The extreme sensitivity of protein synthesis to the inhibition of RNA synthesis, together with the parallel simplifications in the patterns of newly made mRNAs and polypeptides, may imply that only newly made mRNAs are efficiently translated in analog-treated cells.
机译:氨基酸类似物,如其他应激反应效应子一样,在哺乳动物细胞中诱导相同的基因产物,这些产物在热激时被诱导。诱导需要将类似物掺入蛋白质中。我们在这里表明类似物的诱导涉及在转录和翻译水平上运行的控制。新产生的mRNA的电泳图谱随时间而简化,因此推定的应激蛋白mRNA是唯一从细胞核转运的物种。伴随地,蛋白质合成的模式简化了,使得应激蛋白质变成几乎排他的多肽产物。尽管正常的mRNA不被使用或效率大大降低,但当它们被转移到无细胞系统时,它们不会降解并保持可翻译性。诱导应激反应后不久,通过检查多核糖体图谱就证明了多肽链起始的缺陷。长时间暴露后,多核糖体得以恢复,尽管它们几乎只产生应激蛋白,但正常的mRNA仍存在于这些结构中。因此,除了起始缺陷外,还可能涉及伸长病变。蛋白质合成对RNA合成抑制的极端敏感性以及新制备的mRNA和多肽模式的平行简化,可能意味着只有新制备的mRNA在类似物处理的细胞中才能有效翻译。

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