POS0349 SEQUENCE COMPLEMENTARITY BETWEEN SARS-CoV-2 GENOME AND HUMAN NONCODING RNAS ASSOCIATED WITH IMMUNOLOGICAL DISORDERS: AN IN SILICO PIVOTAL STUDY
Authors: R. Talotta, S. Bahrami, M. J. Laska
Journal: Annals of the Rheumatic Diseases (2021)

Background: Recent evidence shows that human cells may produce several noncoding (nc)RNAs in response to viral infections. Among them, a central role has been attributed to long noncoding (lnc)RNAs, more than 200 nucleotides in length, which are also crucially involved in cancer and autoimmunity. LncRNAs epigenetically control the transcription of genes presiding over cell proliferation, differentiation, migration and apoptosis, by directly or indirectly binding cellular or foreign nucleic acids, including viral genomes. Objectives: The objectives of this study were to evaluate in silico the presence of a nucleotide sequence complementarity between the RNA genome of Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) and human ncRNA genes and to analyze any associations between SARS-CoV-2 gene-matching ncRNAs and human diseases. Methods: The FASTA sequence of each of the 11 SARS-CoV-2 isolate Wuhan-Hu-1 genes (ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF10, S, E, M, N) was retrieved from NCBI.nlm.nih.gov/gene (reference sequence NC_045512.2). The ensembl.org library for human ncRNA genes was interrogated for any base-pair match and detected human ncRNAs analyzed for their functional activity. Finally, the associations between ncRNAs and human diseases were searched on GWAS databases ( https://www.ebi.ac.uk/gwas and https://www.genecards.org ). Results: A total of 252 matches between SARS-CoV-2 genes and human ncRNAs were recorded (ORF1ab: 28; ORF3a: 9; ORF6: 50; ORF7a: 31; ORF7b: 16; ORF8: 23; ORF10: 5; S: 24; E: 17; M: 32; N: 17). With the exception of two small nuclear RNAs (RNVU1-4 and RNU4-74P corresponding to ORF6 and ORF10, respectively), all of them were lncRNAs, mostly expressed in testis and central nervous system under physiological conditions. Percentage of alignment ranged from 91.30% to 100%, with a mean nucleotide alignment length of 17.5±2.4. Polymorphic variants of these transcripts have mostly been reported in patients with neuropsychiatric disorders, cancer and dysmetabolism. Of note, we found 13 and 15 complementarities with lncRNAs associated with immune-mediated diseases Table 1. and immunological pathways (IL-2, IL-6, IL-12, IL-12R, IL-13, IL-17, M-CSF, CXCL-10, TRAIL-R2 and IgG glycosylation), respectively. Conclusion: This pivotal study shows that SARS-CoV-2 genes contain complementary sequences to human ncRNAs in turn associated with several diseases, including autoimmunity. The biological effects of this interaction remain to be elucidated. Table 1. SARS-CoV-2 complementary ncRNAs and associated immunological disorders SARS-CoV-2 gene LncRNA Genomic location Nucleotide alignment length Alignment percentage Associated immunological disorder S XACT X:113705866-113705883 18 100% Crohn’s disease N LINC01358 1:59082428-59082574 17 100% Acute Graft-versus-Host Disease E COX10-AS1 17:14029229-14029245 17 100% Systemic lupus erythematosus ORF8 AC093765.3 4:116752764-116752784 21 95.24% Ulcerative colitis ORF6 CDKN2B-AS1 9:22033529-22033546 18 100% Multiple sclerosis CHROMR 2:178433948-178433968 21 95.24% Multiple sclerosis Psoriasis Atopic eczema WAKMAR2 6:137857643-137857657 15 100% Atopic eczema Hay fever Allergic rhinitis Multiple sclerosis Psoriasis Systemic sclerosis Systemic lupus erythematosus Rheumatoid arthritis AC008691.1 5:159362809-159362828 (promoter flank) 20 95% Sarcoidosis Psoriasis Psoriatic arthritis Sclerosing cholangitis Celiac disease Type I diabetes mellitus Systemic lupus erythematosus Juvenile idiopathic arthritis Ulcerative colitis Crohn’s disease Takayasu arteritis Multiple sclerosis LMCD1-AS1 3:7953602-7953616 (enhancer) 15 100% Systemic sclerosis M LINC01934 2:181403969-181403984 16 100% Multiple sclerosis Ankylosing spondylitis Celiac disease Rheumatoid arthritis ORF7b XACT X:113959816-113959831 16 100% Crohn’s disease LINC02621 10:62289643-62302335 15 100% Rheumatoid arthritis LINC01991 3:187966255-187966269 15 100% IgA deficit Atopic asthma Allergic rhinitis Disclosure of Interests: None declared