Department of Chemistry and Health Research Institute, Michigan Technological University, 1400 Townsend Drive, Houghton, MI, 49931, USA.
College of Forest Resources and Environmental Science, Michigan Technological University, 1400 Townsend Drive, Houghton, MI, 49931, USA.
Chembiochem. 2023 Apr 17;24(8):e202300095. doi: 10.1002/cbic.202300095. Epub 2023 Mar 22.
SARS-CoV-2 causes individualized symptoms. Many reasons have been given. We propose that an individual's epitranscriptomic system could be responsible as well. The viral RNA genome can be subject to epitranscriptomic modifications, which can be different for different individuals, and thus epitranscriptomics can affect many events including RNA replication differently. In this context, we studied the effects of modifications including pseudouridine (Ψ), 5-methylcytosine (m C), N6-methyladenosine (m A), N1-methyladenosine (m A) and N3-methylcytosine (m C) on the activity of SARS-CoV-2 replication complex (SC2RC). We found that Ψ, m C, m A and m C had little effect, whereas m A inhibited the enzyme. Both m A and m C disrupt canonical base pairing, but they had different effects. The fact that m A inhibits SC2RC implies that the modification can be difficult to detect. This fact also implies that individuals with upregulated m A including cancer, obesity and diabetes patients might have milder symptoms. However, this contradicts clinical observations. Relevant discussions are provided.
SARS-CoV-2 引起个体症状。人们给出了许多原因。我们提出，个体的转录后修饰系统也可能是原因之一。病毒的 RNA 基因组可能会受到转录后修饰，不同个体的修饰可能不同，因此转录后修饰可以以不同的方式影响包括 RNA 复制在内的许多事件。在这种情况下，我们研究了包括假尿嘧啶 (Ψ)、5-甲基胞嘧啶 (mC)、N6-甲基腺苷 (mA)、N1-甲基腺苷 (mA) 和 N3-甲基胞嘧啶 (mC) 在内的修饰对 SARS-CoV-2 复制复合物 (SC2RC) 活性的影响。我们发现 Ψ、mC、mA 和 mC 几乎没有影响，而 mA 抑制了该酶。mA 和 mC 都破坏了典型的碱基配对，但它们的影响不同。mA 抑制 SC2RC 这一事实意味着这种修饰可能难以检测。这一事实也意味着 mA 上调的个体，包括癌症、肥胖和糖尿病患者，可能症状较轻。然而，这与临床观察相矛盾。提供了相关讨论。
