LSU Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USA.
Alchem Biotech Research, Toronto, ON M5S 1A8, Canada.
Int J Mol Sci. 2023 Feb 8;24(4):3363. doi: 10.3390/ijms24043363.
The severe acute respiratory syndrome -2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5'-methyl cap (mGpppN), a 3'- and 5'-untranslated region (3'-UTR, 5'-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body's natural complement of about ~2650 miRNA species. Depending on host cell and tissue type, in silico analysis, RNA sequencing, and molecular-genetic investigations indicate that, remarkably, almost every single human miRNA has the potential to interact with the primary sequence of SARS-CoV-2 ssvRNA. Individual human variation in host miRNA abundance, speciation, and complexity among different human populations and additional variability in the cell and tissue distribution of the SARS-CoV-2 angiotensin converting enzyme-2 (ACE2) receptor (ACE2R) appear to further contribute to the molecular-genetic basis for the wide variation in individual host cell and tissue susceptibility to COVID-19 infection. In this paper, we review recently described aspects of the miRNA and ssvRNA ribonucleotide sequence structure in this highly evolved miRNA-ssvRNA recognition and signaling system and, for the first time, report the most abundant miRNAs in the control superior temporal lobe neocortex (STLN), an anatomical area involved in cognition and targeted by both SARS-CoV-2 invasion and Alzheimer's disease (AD). We further evaluate important factors involving the neurotropic nature of SARS-CoV-2 and miRNAs and ACE2R distribution in the STLN that modulate significant functional deficits in the brain and CNS associated with SARS-CoV-2 infection and COVID-19's long-term neurological effects.
严重急性呼吸综合征-2（SARS-CoV-2）是 COVID-19 的病原体，它具有一种异常大的正链、单链病毒 RNA（ssvRNA）基因组，约为29903 个核苷酸（nt）。在许多方面，这种 ssvRNA 类似于一种非常大的、多顺反子信使 RNA（mRNA），具有 5'-甲基化帽（mGpppN）、3'-和 5'-非翻译区（3'-UTR、5'-UTR）和多聚腺苷酸化（poly-A+）尾巴。因此，SARS-CoV-2 ssvRNA 容易受到小非编码 RNA（sncRNA）和/或 microRNA（miRNA）的靶向作用，以及通过人体约2650 种 miRNA 种类的天然补体中和/或抑制其感染力。根据宿主细胞和组织类型，计算机分析、RNA 测序和分子遗传学研究表明，令人惊讶的是，几乎每一种人类 miRNA 都有可能与 SARS-CoV-2 ssvRNA 的原始序列相互作用。宿主 miRNA 丰度、物种形成和不同人群之间的复杂性以及 SARS-CoV-2 血管紧张素转换酶-2（ACE2R）受体在细胞和组织中的分布的个体差异，似乎进一步促成了个体宿主细胞和组织对 COVID-19 感染易感性的分子遗传学基础的多样性。在本文中，我们回顾了最近描述的 miRNA 和 ssvRNA 核苷酸序列结构的方面，在这个高度进化的 miRNA-ssvRNA 识别和信号系统中，首次报告了控制优势颞叶新皮质（STLN）中最丰富的 miRNA，这是一个参与认知的解剖区域，也是 SARS-CoV-2 入侵和阿尔茨海默病（AD）的靶点。我们进一步评估了涉及 SARS-CoV-2 的神经毒性性质和 miRNA 以及 ACE2R 在 STLN 中的分布的重要因素，这些因素调节了与 SARS-CoV-2 感染和 COVID-19 的长期神经影响相关的大脑和中枢神经系统的显著功能缺陷。
