Oxidative Damage to RNA is Altered by the Presence of Interacting Proteins or Modified Nucleosides.

Oxidative Damage to RNA is Altered by the Presence of Interacting Proteins or Modified Nucleosides.
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DOI:
10.3389/fmolb.2021.697149
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发表时间:
2021
影响因子:
5
通讯作者:
Addepalli B
Addepalli B
中科院分区:
生物学3区
文献类型:
--
作者:
Estevez M;Valesyan S;Jora M;Limbach PA;Addepalli B

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由Fenton反应(化学)或UVR暴露(照片)引发的氧化应激可通过核苷酸的氧化损伤包括RNA在内的细胞生物分子。除了这种异种化学修饰外,RNA还包含几种转录后核苷修饰,这些修饰由酶安装,以调节结构、RNA-蛋白质相互作用和生化功能。我们研究了两种不同环境下细胞蛋白质合成所需的天然修饰RNA的氧化损伤程度。当RNA与蛋白质不相关时,氧化损伤的程度较高,但当RNA以核糖核蛋白复合体的形式出现时,损伤程度较低,例如完整的核糖体。我们的研究还表明,核糖体RNA中特定位置的甲基化缺失可能会使其更容易受到光氧化应激的影响。然而,鸟苷的氧化程度因修饰缺失的位置而不同,这表明了位置依赖的结构效应。此外,缺乏5-甲氨甲基-2-硫代尿苷(Mnm5s2U)(存在于赖氨酸和谷氨酸tRNA反义密码子中)的大肠杆菌菌株比其野生型菌株更容易受到RNA氧化损伤,这表明mnm5s2U修饰具有辅助功能。这些研究表明,细胞内存在酶修饰的核苷或蛋白质结合,可改变对RNA的氧化损伤。
Oxidative stress triggered by the Fenton reaction (chemical) or UVR exposure (photo) can damage cellular biomolecules including RNA through oxidation of nucleotides. Besides such xenobiotic chemical modifications, RNA also contains several post-transcriptional nucleoside modifications that are installed by enzymes to modulate structure, RNA-protein interactions, and biochemical functions. We examined the extent of oxidative damage to naturally modified RNA which is required for cellular protein synthesis under two different contexts. The extent of oxidative damage is higher when RNA is not associated with proteins, but the degree of damage is lower when the RNA is presented in the form of a ribonucleoprotein complex, such as an intact ribosome. Our studies also indicate that absence of methylations in ribosomal RNA at specific positions could make it more susceptible to photooxidative stress. However, the extent of guanosine oxidation varied with the position at which the modification is deficient, indicating position-dependent structural effects. Further, an E. coli strain deficient in 5-methylaminomethyl-2-thiouridine (mnm5s2U) (found in lysine and glutamate tRNA anticodon) is more vulnerable to oxidative RNA damage compared to its wildtype strain suggesting an auxiliary function for the mnm5s2U modification. These studies indicate that oxidative damage to RNA is altered by the presence of enzymatic modified nucleosides or protein association inside the cell.
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