Department of Biology, Washington University in St. Louis, St. Louis, United States.
Elife. 2020 Sep 17;9:e61984. doi: 10.7554/eLife.61984.
Similar to DNA replication, translation of the genetic code by the ribosome is hypothesized to be exceptionally sensitive to small chemical changes to its template mRNA. Here we show that the addition of common alkylating agents to growing cultures of leads to the accumulation of several adducts within RNA, including N(1)-methyladenosine (mA). As expected, the introduction of mA to model mRNAs was found to reduce the rate of peptide bond formation by three orders of magnitude in a well-defined in vitro system. These observations suggest that alkylative stress is likely to stall translation in vivo and necessitates the activation of ribosome-rescue pathways. Indeed, the addition of alkylation agents was found to robustly activate the transfer-messenger RNA system, even when transcription was inhibited. Our findings suggest that bacteria carefully monitor the chemical integrity of their mRNA and they evolved rescue pathways to cope with its effect on translation.
与 DNA 复制类似，核糖体对遗传密码的翻译被假设对其模板 mRNA 的微小化学变化非常敏感。在这里，我们表明，向生长中的添加常见烷化剂会导致 RNA 内积累几种加合物，包括 N(1)-甲基腺苷（mA）。正如预期的那样，在一个明确定义的体外系统中，向模型 mRNA 中引入 mA 被发现将肽键形成的速率降低了三个数量级。这些观察结果表明，烷化应激很可能使体内翻译停滞，并需要激活核糖体救援途径。事实上，即使转录被抑制，添加烷化剂也被发现能够强烈激活转移信使 RNA 系统。我们的发现表明，细菌会仔细监测其 mRNA 的化学完整性，并且它们已经进化出救援途径来应对其对翻译的影响。
