State University of New York Polytechnic Institute, College of Arts & Sciences, Utica, NY, USA.
State University of New York Polytechnic Institute, College of Nanoscale Science & Engineering, Albany, NY, USA.
Future Med Chem. 2019 Apr;11(8):885-900. doi: 10.4155/fmc-2018-0404. Epub 2019 Feb 12.
Transfer RNAs (tRNAs) undergo extensive chemical modification within cells through the activity of tRNA methyltransferase enzymes (TRMs). Although tRNA modifications are dynamic, how they impact cell behavior after stress and during tumorigenesis is not well understood. This review discusses how tRNA modifications influence the translation of codon-biased transcripts involved in responses to oxidative stress. We further discuss emerging mechanistic details about how aberrant TRM activity in cancer cells can direct programs of codon-biased translation that drive cancer cell phenotypes. The studies reviewed here predict future preventative therapies aimed at augmenting TRM activity in individuals at risk for cancer due to exposure. They further predict that attenuating TRM-dependent translation in cancer cells may limit disease progression while leaving noncancerous cells unharmed.
转移 RNA（tRNA）在细胞内通过 tRNA 甲基转移酶（TRM）的活性发生广泛的化学修饰。尽管 tRNA 修饰是动态的，但它们在应激后和肿瘤发生过程中如何影响细胞行为还不是很清楚。本综述讨论了 tRNA 修饰如何影响参与氧化应激反应的密码子偏倚转录物的翻译。我们进一步讨论了关于癌细胞中异常 TRM 活性如何指导密码子偏倚翻译程序从而驱动癌细胞表型的新的机制细节。这里回顾的研究预测了未来的预防疗法，旨在增强因暴露而处于癌症风险中的个体的 TRM 活性。它们进一步预测，在不伤害非癌细胞的情况下，抑制癌细胞中依赖 TRM 的翻译可能会限制疾病的进展。
