Transcription of the Envelope Protein by 1-L Protein-RNA Recognition Code Leads to Genes/Proteins That Are Relevant to the SARS-CoV-2 Life Cycle and Pathogenesis.

Jozef Nahalka

doi:10.3390/cimb44020055

Abstract

The theoretical protein–RNA recognition code was used in this study to research the compatibility of the SARS-CoV-2 envelope protein (E) with mRNAs in the human transcriptome. According to a review of the literature, the spectrum of identified genes showed that the virus post-transcriptionally promotes or represses the genes involved in the SARS-CoV-2 life cycle. The identified genes/proteins are also involved in adaptive immunity, in the function of the cilia and wound healing (EMT and MET) in the pulmonary epithelial tissue, in Alzheimer’s and Parkinson’s disease and in type 2 diabetes. For example, the E-protein promotes BHLHE40, which switches off the IL-10 inflammatory “brake” and inhibits antiviral THαβ cells. In the viral cycle, E supports the COPII-SCAP-SREBP-HSP90α transport complex by the lowering of cholesterol in the ER and by the repression of insulin signaling, which explains the positive effect of HSP90 inhibitors in COVID-19 (geldanamycin), and E also supports importin α/β-mediated transport to the nucleus, which explains the positive effect of ivermectin, a blocker of importins α/β. In summary, transcription of the envelope protein by the 1-L protein–RNA recognition code leads to genes/proteins that are relevant to the SARS-CoV-2 life cycle and pathogenesis.

Highlights

Whether the molecular RNA world existed or not, RNA represents the central molecule “software” and “hardware”, from the primary proto-cells to today’s eukaryotic cells
The 1-L protein–RNA recognition code means that RNA-binding proteins (RBPs) use at least one amino acid sequence that is exactly compatible with the RNA nucleotide sequences according to the key one amino acid per nucleotide (1-L), and the nucleotide is defined by the type of nucleotide at the second position in the amino acid codon
Throughout the whole study, it was considered that the viral structural protein E sequence is compatible with the mRNA of the protein host genes or with the host regulation microRNAs, and this was based on the protein–RNA recognition code

Summary

Introduction

Whether the molecular RNA world existed or not, RNA represents the central molecule “software” (pre-mRNA) and “hardware” (e.g., ribosome), from the primary proto-cells to today’s eukaryotic cells. Proteins that bind RNA, RNA-binding proteins (RBPs), participate in the formation of ribonucleoprotein complexes (RNPs), and RNPs orchestrate mRNA maturation and protein translation processes. Besides participating in large RNP machines, spliceosomes and ribosomes, various RBPs can recognize hundreds of transcripts and form extensive regulatory networks that help to maintain cell homeostasis [1]. Improperly processed RNA usually contains repeat sequences consisting of three to six nucleotides, which sequester RBPs specialized in the repeated sequence motifs [7] or initiates RAN translation (repeat-associated non-ATG), leading to toxic proteins [8]. The (GGGGCC)n hexanucleotide repeat expansion in intron 1 of C9orf is a major cause of ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia) and the (GGGGCC)n sequester hnRNP H RBP [7]

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Conclusion