Haddad Hazem
Princess Haya Biotechnology Centre, Jordan University of Science and Technology, Irbid, Jordan.
Department of Biomedical Engineering, School of Applied Medical Sciences, German Jordanian University, Amman, Jordan.
Noncoding RNA Res. 2020 Sep;5(3):135-143. doi: 10.1016/j.ncrna.2020.08.002. Epub 2020 Aug 20.
MicroRNAs (miRNAs) are non-coding RNAs that control many functions within the human cells by controlling protein levels through binding to messenger RNA (mRNA) translation process or mRNA abundance. Many pieces of evidence show that miRNAs affect the viral RNA replication and pathogenesis through direct binding to the RNA virus to mediate changes in the host transcriptome. Many previous studies have been studying the interaction between human cells' miRNA and viral RNA to predict many targets along the viral genome. In this work, via the miRDB database, we determined the target scores of predicted human miRNA to bind with the ss-RNA of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) in general and its spike gene in specific. Our predicted miRNA targets of the ss-RNA of SARS-CoV-2 might destabilize the ss-RNA translation of SARS-CoV-2 that has been established by more than 80% of asymptomatic infected cases in Jordan due to host miRNA interactions. In respiratory epithelial cells, the high prediction scoring for miRNAs covers the RNA from 5' to 3' that explains successful antiviral defenses against ss-RNA of SARS-CoV-2 and might lead to new nucleotide deletion mechanisms. The exciting findings here that the nucleotide substitution 1841A > G at the viral genomic RNA level, which is an amino acid substation D614G at the spike protein level showed a change in the predicted miRNA sequence from hsa-miR-4793-5p to hsa-miR-3620-3p with an increase in the target score from 91 to 92.
微小RNA(miRNA)是非编码RNA,通过与信使RNA(mRNA)翻译过程或mRNA丰度结合来控制蛋白质水平,从而调控人类细胞内的多种功能。许多证据表明,miRNA通过直接与RNA病毒结合来影响病毒RNA复制和发病机制,进而介导宿主转录组的变化。此前许多研究一直在探讨人类细胞miRNA与病毒RNA之间的相互作用,以预测病毒基因组上的多个靶点。在这项研究中,我们通过miRDB数据库确定了预测的人类miRNA与严重急性呼吸综合征冠状病毒(SARS-CoV-2)的单链RNA(ss-RNA)及其特定刺突基因结合的靶点分数。我们预测的SARS-CoV-2单链RNA的miRNA靶点可能会破坏SARS-CoV-2的单链RNA翻译,约旦超过80%的无症状感染病例正是由于宿主miRNA相互作用而建立了这种单链RNA翻译。在呼吸道上皮细胞中,miRNA的高预测分数覆盖了从5'到3'的RNA,这解释了针对SARS-CoV-2单链RNA成功的抗病毒防御机制,并且可能导致新的核苷酸缺失机制。此处令人兴奋的发现是,病毒基因组RNA水平上的核苷酸替换1841A>G,即刺突蛋白水平上的氨基酸替换D614G,导致预测的miRNA序列从hsa-miR-4793-5p变为hsa-miR-3620-3p,靶点分数从91增加到92。