Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, United States of America.
Department of Biological Sciences, University of Cincinnati, Cincinnati, Ohio, United States of America.
PLoS One. 2022 Mar 29;17(3):e0266239. doi: 10.1371/journal.pone.0266239. eCollection 2022.
Cryptococcus neoformans is a fungus that is able to survive abnormally high levels of ionizing radiation (IR). The radiolysis of water by IR generates reactive oxygen species (ROS) such as H2O2 and OH-. C. neoformans withstands the damage caused by IR and ROS through antioxidant production and enzyme-catalyzed breakdown of ROS. Given these particular cellular protein needs, questions arise whether transfer ribonucleic acids molecules (tRNAs) undergo unique chemical modifications to maintain their structure, stability, and/or function under such environmental conditions. Here, we investigated the effects of IR and H2O2 exposure on tRNAs in C. neoformans. We experimentally identified the modified nucleosides present in C. neoformans tRNAs and quantified changes in those modifications upon exposure to oxidative conditions. To better understand these modified nucleoside results, we also evaluated tRNA pool composition in response to the oxidative conditions. We found that regardless of environmental conditions, tRNA modifications and transcripts were minimally affected. A rationale for the stability of the tRNA pool and its concomitant profile of modified nucleosides is proposed based on the lack of codon bias throughout the C. neoformans genome and in particular for oxidative response transcripts. Our findings suggest that C. neoformans can rapidly adapt to oxidative environments as mRNA translation/protein synthesis are minimally impacted by codon bias.
新生隐球菌是一种能够在异常高剂量电离辐射（IR）下存活的真菌。IR 会使水发生辐射分解，产生活性氧（ROS），如 H2O2 和 OH-。新生隐球菌通过抗氧化剂的产生和酶促分解 ROS 来抵抗 IR 和 ROS 造成的损伤。鉴于这些特殊的细胞蛋白需求，人们不禁会产生疑问，在这种环境条件下，转移核糖核酸（tRNA）分子是否会发生独特的化学修饰，以维持其结构、稳定性和/或功能。在这里，我们研究了 IR 和 H2O2 暴露对新生隐球菌 tRNA 的影响。我们通过实验鉴定了新生隐球菌 tRNA 中存在的修饰核苷，并量化了在暴露于氧化条件下这些修饰的变化。为了更好地理解这些修饰核苷的结果，我们还评估了 tRNA 池组成对氧化条件的响应。我们发现，无论环境条件如何，tRNA 修饰和转录物都受到最小的影响。基于新生隐球菌基因组中缺乏密码子偏向性，特别是在氧化反应转录物中，提出了 tRNA 池稳定性及其伴随的修饰核苷特征的合理化解释。我们的研究结果表明，新生隐球菌可以迅速适应氧化环境，因为 mRNA 翻译/蛋白质合成受到密码子偏向性的影响最小。
