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Review
. 2024 Dec;15(1):2350182.
doi: 10.1080/19491034.2024.2350182. Epub 2024 May 13.

LncRNAs, nuclear architecture and the immune response

Christy Montano  1 , Cristina Flores-Arenas  1 , Susan Carpenter  1
Affiliations
Review

LncRNAs, nuclear architecture and the immune response

Christy Montano et al. Nucleus. 2024 Dec.

Abstract

Long noncoding RNAs (LncRNAs) are key regulators of gene expression and can mediate their effects in both the nucleus and cytoplasm. Some of the best-characterized lncRNAs are localized within the nucleus, where they modulate the nuclear architecture and influence gene expression. In this review, we discuss the role of lncRNAs in nuclear architecture in the context of their gene regulatory functions in innate immunity. Here, we discuss various approaches to functionally characterize nuclear-localized lncRNAs and the challenges faced in the field.

Keywords: Chromatin; innate immunity; long noncoding RNAs; macrophages; nucleus.

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Conflict of interest statement

S. C. is a paid consultant for NextRNA Therapeutics.

Figures

Fig 1 outlines the mechanisms of immune gene regulation by nuclear-localized lncRNAs. Focusing on the nucleus, we highlight the role of the three lncRNAs. XIST functions as a ligand to stimulate TLR7 and induce type 1 interferons. NEAT1 is required for paraspeckle formation upon viral infection, inducing the release of IL8, and lncRNAs, including lincRNA-Cox2, LOUP, UMLILO, and AMANZI, function in cis to regulate neighboring genes within topologically associating domains.
Figure 1.
Mechanisms of immune gene regulation by nuclear-localized lncRNAs. a, female-specific X-inactive specific transcript (XIST) is a rich source of TLR7 ligands and consequent activation. XIST harbors a GUCCUUAA motif that induces TLR7. This proinflammatory role of XIST is found to be most common in women with systemic lupus erythematous (SLE), possibly explaining why women are more likely to be affected by SLE. b, Nuclear enriched abundant transcript 1 (NEAT1) is essential to forming paraspeckles in the nucleus and inducing antiviral cytokine production upon viral infection. NEAT1 transcription is increasingly induced upon viral infection, producing excess paraspeckle formation in the nucleus and inducing IL8 production. c, 3D chromatin looping allows lncRNAs to regulate immune genes in cis. Upstream master lncRNA of the inflammatory chemokine locus (UMLILO) directs transcription factors across chemokine promoters, enabling epigenetic priming for their transcription. LincRNA-Cox2 is a multifunctional locus that can regulate Ptgs2 through an enhancer mechanism.
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