The c-fos proto-oncogene provides a good system to study the processes underlying messenger RNA degradation. After growth factor stimulation of susceptible cells, the c-fos transcription rate transiently increases from a low basal level by as much as 50-fold, producing a large amount of exceedingly unstable c-fos mRNA that is rapidly degraded. Here, we investigate the c-fos mRNA degradation process, and find that: (1) ongoing translation of the c-fos mRNA itself is required for its degradation; (2) after synthesis, the mRNA poly(A) tail is rapidly removed, in a translation-dependent manner, leading to accumulation of apparently deadenylated RNA; (3) deletion or replacement of an AU-rich sequence at the mRNA 3' end significantly stabilizes the mRNA; (4) deletion of the 3' AU-rich sequences dramatically slows the poly(A) shortening rate. These results suggest that the 3' AU-rich sequences act to destabilize the mRNA by directing rapid removal of the mRNA poly(A) tract.

译文

:c-fos原癌基因提供了一个很好的系统,用于研究信使RNA降解的基础过程。在易感细胞的生长因子刺激后,c-fos转录速率从低基础水平瞬时增加了多达50倍,从而产生了大量极其不稳定的c-fos mRNA,并迅速降解。在这里,我们研究了c-fos mRNA的降解过程,发现:(1)c-fos mRNA本身的持续翻译对其降解是必需的; (2)合成后,以翻译依赖性方式快速去除mRNA poly(A)尾巴,导致明显的去腺苷酸化的RNA积累。 (3)在mRNA 3'末端缺失或替换富含AU的序列可显着稳定mRNA; (4)删除富含3'AU的序列会大大减慢poly(A)的缩短速度。这些结果表明,富含3'AU的序列通过指导快速去除mRNA poly(A)束而使mRNA不稳定。

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