The Role Of Long Non-Coding RNAs In COVID-19

COVID-19 News: In the intricate web of host-pathogen interactions, the role of long non-coding RNAs (lncRNAs) has emerged as a crucial player, influencing disease severity, progression, and outcomes. Specifically, during the COVID-19 pandemic caused by the SARS-CoV-2 virus, researchers at the CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) in Delhi, India, delved into the cell-specific housekeeping functions of lncRNAs in both infected and recovered individuals. This comprehensive study covered in this COVID-19 News report, aimed to understand the spatio-temporal expression dynamics of lncRNAs, shedding light on their functional roles during and after SARS-CoV-2 infection.


Graphical Abstract - Cell-specific housekeeping role of lncRNAs in COVID-19-infected and recovered patients

Thailand Medical News had previously covered some studies that showed the role of certain lncRNAs in COVID-19 infection and pathogenesis.
 
https://www.thailandmedical.news/news/harvard-study-finds-that-cognition-associated-long-noncoding-rnas-are-dysregulated-upon-severe-covid-19
 
https://www.thailandmedical.news/news/breaking-news-u-s-study-reveals-a-fascinating-role-of-long-noncoding-rna-snhg15-in-aiding-sars-cov-2-cell-entry-via-oncogene-rabl2a
 
https://www.thailandmedical.news/news/breaking-news-study-finds-that-human-host-lncrnas-and-mirnas-play-a-role-in-antiviral-response-in-sars-cov-2-infection
 
https://www.thailandmedical.news/news/a-compelling-look-at-long-non-coding-rna-malat1-s-role-in-lung-diseases,-including-covid-19
 
The Dynamics of lncRNA Expression in COVID-19
The study employed single-cell RNA sequencing (RNA-seq) to investigate the expression patterns of lncRNAs across healthy, SARS-CoV-2-infected, and recovered individuals. The researchers identified 203 differentially expressed lncRNAs, including cell type-specific ones such as MALAT1, NEAT1, ZFAS1, SNHG7, SNHG8, and SNHG25, modulating immune function in various cell types.

Interestingly, among these differentially expressed lncRNAs, some remained invariant, exhibiting no significant change in expression across conditions. These invariant lncRNAs were found to play essential housekeeping roles in infected and recovered individuals, emphasizing their import ance in the disease context.
 
Functional Insights into lncRNA Activities
The study focused on understanding the functional duet between lncRNAs and mRNAs within diverse cell types during infection. It emphasized that while protein-coding genes and surface markers have been the main focus in previous studies, exploring the specific role of lncRNAs is crucial for a comprehensive understanding of the immune response during infection.
 
The researchers revealed that lncRNAs, such as EGOT, can have both positive and negative effects on the host response to pathogens. EGOT, for example, antagonizes the antiviral response and promotes viral proliferation in the case of hepatitis-C virus (HCV). Similarly, NEAT1 has varied effects on different viruses, inhibiting HIV replication while enhancing HSV replication. This dual nature of lncRNAs in influencing the immune response adds complexity to their role in infectious diseases.
 
Single-Cell Genomics Unveiling Host-Pathogen Interactions
Single-cell genomics provided granular insights into host-pathogen interactions, showcasing the spatio-temporal expression patterns of lncRNAs. Investigations using blood-derived peripheral blood mononuclear cells (PBMCs) from COVID-19 patients demonstrated upregulated interferon (IFN)-stimulated genes (ISGs) in various cell types, revealing the antiviral activities of these cells. The study further highlighted the dysregulated immunological interaction, including downregulation of human leukocyte antigen (HLA)-II genes and elevated expression of inflammatory cytokines and proinflammatory molecules.
 
Differential Responses and Outcomes in COVID-19
Despite the commonality of SARS-CoV-2 infection, individuals exhibited varying disease severities, ranging from mild to severe. The study emphasized the importance of understanding not only how the host responds to the infection but also why similar groups of people with the same pathogen challenge experience different disease outcomes.
 
The investigation extended to post-SARS-CoV-2 infection responses in recovered individuals, revealing heightened inflammatory responses, loss of B cell maturation, and T cell exhaustion. The dynamics of host responses in recovered patients are yet to be fully understood, and the study aimed to bridge this gap by exploring the role of lncRNAs in recovered individuals.
 
Two Faces of lncRNA Expression
The study identified two distinct patterns of lncRNA expression: variant and invariant. The variant lncRNAs primarily regulated immune responses, contributing to the modulation of pathways like TGF beta, mTORC1, and PI3K/AKT/mTOR signaling during infection. On the other hand, invariant lncRNAs, such as UCA1, SNHG18, SNHG27, SNHG28, ROR1-AS1, HOTAIR, and NRAV, maintained essential housekeeping functions across healthy, infected, and recovered individuals.
 
Cell Types and Regulatory Mechanisms
The study pinpointed specific cell types, including class-switched memory B cells, naive B cells, classical monocytes, NK T cells, NK cells, and platelets, as key contributors to the regulation of invariant lncRNA-mediated housekeeping functions. Intriguingly, while both variant and invariant lncRNAs exhibited comparable repeat element abundance, variant lncRNAs displayed higher Alu content, suggesting increased interactions with proximal and distal genes crucial for immune response modulation.
 
The Alu-Mediated Regulatory Landscape
Alu elements, known for their role in lncRNA-mRNA interactions, were found to be more abundant in variant lncRNAs. This heightened Alu content in variant lncRNAs indicated a dynamic regulation involving increased interactions with adjacent genes, essential for immune response modulation. The study also suggested a potential interaction between HOTAIR and HNRNPA1, revealing shared regulatory mechanisms for both variant and invariant lncRNAs.
 
Implications for Future Research
Despite the progress made in understanding the role of lncRNAs in infectious diseases, including COVID-19, the study emphasized the scarcity of research focusing on single-cell resolved lncRNA responses in different disease contexts. The findings shed light on the need for exploring the entire non-coding transcriptome, including non-polyadenylated RNAs, to uncover additional cell-type-specific functions.
 
Additionally, the researchers acknowledged the importance of validating the identified genes through qPCR, which was challenging due to limitations in obtaining a sufficient quantity of clinical samples during the early phase of the COVID-19 pandemic. Future studies should consider longitudinal analyses after recovery to validate the immune dynamics highlighted in recovered COVID-19 patients.
 
Conclusion
In conclusion, the study offers a thorough insight into the cell type-specific functions of lncRNAs during and after COVID-19 at a single-cell resolution. The identification of variant and invariant lncRNAs, their regulatory mechanisms, and their distinct roles in immune response modulation and housekeeping functions provide a foundation for future research in understanding the maintenance of homeostasis during and after SARS-CoV-2 infection. The study calls for continued exploration of the intricate world of lncRNAs and their implications in infectious diseases, ultimately contributing to advancements in therapeutic strategies and personalized medicine.
 
The study findings were published in the peer reviewed journal: NAR Genomics & Bioinformatics. (Oxford Academic).
https://academic.oup.com/nargab/article/6/1/lqae023/7616357
 
For the latest COVID-19 News, keep on logging to Thailand Medical News.