LncRNAs harbouring regulatory motifs within repeat elements modulate immune response towards COVID‐19 disease severity and clinical outcomes

Chattopadhyay, Partha; Mishra, Pallavi; Khare, Kriti; Yadav, Aanchal; Mehta, Priyanka; Saifi, Sheeba; Swaminathan, Aparna; Devi, Priti; Parveen, Shaista; Tyagi, Akansha; Jha, Vinita; Tarai, Bansidhar; Jha, Sujeet Kumar; Budhiraja, Sandeep; Narayan, Jitendra; Pandey, Rajesh

doi:10.1002/ctm2.932

Cited by 5 publications

(10 citation statements)

References 17 publications

(13 reference statements)

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“…Besides, high repeat element abundance is a feature of the lncRNAs. Our previous study as well as few other groups also highlight the role of repeat elements in the infectious disease and its association with disease severity [8,11,33,34]. Previously, we have also shown that in severe COVID-19, repeat element abundance within the DE lncRNAs are higher than their global abundance within the lncRNAs (8).…”

Section: Discussionsupporting

confidence: 52%

“…In our previous study, we have highlighted lncRNAmediated immune responses modulating COVID-19 differential disease severities (8). Notably, four lncRNAs, lnc-FAM153C-5:15, ROR1-AS1:6, LINC01684:22, and UGDH-AS1:11 upregulated in the VBT group, were downregulated in the Severe group compared to Mild or Moderate (Figure 7B).…”

Section: Discussionmentioning

confidence: 79%

“…Differential abundance of repeat elements is one of the major features of the lncRNAs. Moreover, lncRNAs often modulate gene expression through repeat elements present within the lncRNA sequences (8). Therefore, to understand the role of repeat element-based modulation of the lncRNA functions, we looked at the repeat element distribution within the interacting lncRNAs (n=34) discovered from the co-expression network.…”

Section: Repeat Elements Within Lncrnas As Possible Modulators Of Lnc...mentioning

confidence: 99%

“…Long noncoding RNAs (lncRNAs), as a key component of the human transcriptome, and because of their gene regulatory role, are crucial factors to explore/elucidate in order to understand the variable host response in the vaccine breakthrough infection. Furthermore, prior research by our lab and others has emphasized the function of lncRNAs in the SARS-CoV-2 infection and how it influences differential disease severities (8)(9)(10). Therefore, we conducted this first-of-its-kind study to understand the role of lncRNAs in the vaccination breakthrough infection, which might explain why despite the vaccination, the individuals were infected with the SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 98%

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Transcriptomic study reveals lncRNA-mediated downregulation of innate immune and inflammatory response in the SARS-CoV-2 vaccination breakthrough infections

et al. 2022

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IntroductionThe emergence of multiple variants of concerns (VOCs) with higher number of Spike mutations have led to enhanced immune escape by the SARS-CoV-2. With the increasing number of vaccination breakthrough (VBT) infections, it is important to understand the possible reason/s of the breakthrough infections.MethodsWe performed transcriptome sequencing of 57 VBT and unvaccinated COVID-19 patients, followed by differential expression and co-expression analysis of the lncRNAs and the mRNAs. The regulatory mechanism was highlighted by analysis towards repeat element distribution within the co-expressed lncRNAs, followed by repeats driven homologous interaction between the lncRNAs and the promoter regions of genes from the same topologically associated domains (TAD).ResultsWe identified 727 differentially expressed lncRNAs (153 upregulated and 574 downregulated) and 338 mRNAs (34 up- and 334 downregulated) in the VBT patients. This includes LUCAT1, MALAT1, ROR1-AS1, UGDH-AS1 and LINC00273 mediated modulation of immune response, whereas MALAT1, NEAT1 and GAS5 regulated inflammatory response in the VBT. LncRNA-mRNA co-expression analysis highlighted 34 lncRNAs interacting with 267 mRNAs. We also observed a higher abundance of Alu, LINE1 and LTRs within the interacting lncRNAs of the VBT patients. These interacting lncRNAs have higher interaction with the promoter region of the genes from the same TAD, compared to the non-interacting lncRNAs with the enrichment of Alu and LINE1 in the gene promoter.DiscussionSignificant downregulation and GSEA of the TAD gene suggest Alu and LINE1 driven homologous interaction between the lncRNAs and the TAD genes as a possible mechanism of lncRNA-mediated suppression of innate immune/inflammatory responses and activation of adaptive immune response. The lncRNA-mediated suppression of innate immune/inflammatory responses and activation of adaptive immune response might explain the SARS-CoV-2 breakthrough infections with milder symptoms in the VBT. Besides, the study also highlights repeat element mediated regulation of genes in 3D as another possible way of lncRNA-mediated immune-regulation modulating vaccination breakthroughs milder disease phenotype and shorter hospital stay.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 79%

Section: Repeat Elements Within Lncrnas As Possible Modulators Of Lnc...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Transcriptomic study reveals lncRNA-mediated downregulation of innate immune and inflammatory response in the SARS-CoV-2 vaccination breakthrough infections

et al. 2022

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“…And this new model of RIG-I recognition does not stimulate its ATPase ( Yamada et al., 2021 ). In addition, lncRNAs are differentially expressed in terms of their levels in SARS-CoV-2 infection cells ( Devadoss et al., 2021 ; Chattopadhyay et al., 2022 ). In contrast to the 3’-region of the SARS-CoV-2 genome, the 5’-region is capable of interacting with several human lncRNAs ( Moazzam-Jazi et al., 2021 ).…”

Section: Lncrnas Regulate the Rig-i Signaling Pathway In Covid-19 Inf...mentioning

confidence: 99%

The lncRNAs involved in regulating the RIG-I signaling pathway

Liu

Cao

et al. 2022

Front. Cell. Infect. Microbiol.

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Understanding the targets and interactions of long non-coding RNAs (lncRNAs) related to the retinoic acid-inducible gene-I (RIG-I) signaling pathway is essential for developing interventions, which would enable directing the host inflammatory response regulation toward protective immunity. In the RIG-I signaling pathway, lncRNAs are involved in the important processes of ubiquitination, phosphorylation, and glycolysis, thus promoting the transport of the interferon regulatory factors 3 and 7 (IRF3 and IRF7) and the nuclear factor kappa B (NF-κB) into the nucleus, and activating recruitment of type I interferons (IFN-I) and inflammatory factors to the antiviral action site. In addition, the RIG-I signaling pathway has recently been reported to contain the targets of coronavirus disease-19 (COVID-19)-related lncRNAs. The molecules in the RIG-I signaling pathway are directly regulated by the lncRNA–microRNAs (miRNAs)–messenger RNA (mRNA) axis. Therefore, targeting this axis has become a novel strategy for the diagnosis and treatment of cancer. In this paper, the studies on the regulation of the RIG-I signaling pathway by lncRNAs during viral infections and cancer are comprehensively analyzed. The aim is to provide a solid foundation of information for conducting further detailed studies on lncRNAs and RIG-I in the future and also contribute to clinical drug development.

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Identification of a novel prognostic cuproptosis-associated LncRNA signature for predicting prognosis and immunotherapy response in patients with esophageal cancer

Sun,

Li,

Yang

et al. 2024

Heliyon

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LncRNAs harbouring regulatory motifs within repeat elements modulate immune response towards COVID‐19 disease severity and clinical outcomes

Cited by 5 publications

References 17 publications

Transcriptomic study reveals lncRNA-mediated downregulation of innate immune and inflammatory response in the SARS-CoV-2 vaccination breakthrough infections

Transcriptomic study reveals lncRNA-mediated downregulation of innate immune and inflammatory response in the SARS-CoV-2 vaccination breakthrough infections

The lncRNAs involved in regulating the RIG-I signaling pathway

Identification of a novel prognostic cuproptosis-associated LncRNA signature for predicting prognosis and immunotherapy response in patients with esophageal cancer

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