lncRNAs and immunity – watchdogs for host pathogen interactions

Immune responses combat various infectious agents by inducing inflammatory responses, antimicrobial pathways and adaptive immunity. The polygenic responses to these external stimuli are temporally and coordinately regulated. Specific lncRNAs are induced to modulate innate and adaptive immune responses which can function through various target interactions like RNA-DNA, RNA-RNA, and RNA-protein interaction and hence affect the immunogenic regulation at various stages of gene expression. LncRNA are found to be present in various immune cells like monocytes, macrophages, dendritic cells, neutrophils, T cells and B cells. They have been shown to be involved in many biological processes, including the regulation of the expression of genes, the dosage compensation and genomics imprinting, but the knowledge how lncRNAs are regulated and how they alter cell differentiation/function is still obscure. Further dysregulation of lncRNA has been seen in many diseases, but as yet very less research has been carried out to understand the role of lncRNAs in regulation during host-pathogens interactions. Researchers from the Sher-e-Kashmir University of Agricultural Sciences and Technology summarize the functional developments and mechanism of action of lncRNAs, in immunity and defense of host against pathogens.

Different types of pathogens, including viruses infect the host and then induce functional lncRNAs in host, which have been studied to control and modulate the pathogen infections

lncRNA

The viral lncRNA PAN suppresses expression of host genes involved in the inflammatory and antiviral responses, including IFNγ, IL-18, IFNA16, and RNase L. A recent report showed that PAN can physically interact with polycomb group proteins, such as PRC2 and mediate repression of host cellular gene expression. On the other hand, lncRNA NRAV also has an inhibitory role in initial transcription of multiple interferon-stimulated genes (ISGs), such as MxA and IFITM3, via epigenetically regulating histone modifications of these genes. NEAT1 is shown to bind to SFPQ (a paraspeckle protein) and play an important role in formation of nuclear paraspeckle body. Recently, a study demonstrated that SFPQ silences IL-8 expression via binding to IL-8 promoter in normal physiological states. NFAT is a highly phosphorylated transcriptional factor present in the cytoplasm of resting cells. NFAT is dephosphorylated and transported from the cytoplasm into the nucleus in response to calcium-dependent signals, to induce expression of target genes such as IL-2, which plays a key role in enduring cell-mediated immunity

Mumtaz PT, Bhat SA, Ahmad SM, Dar MA, Ahmed R, Urwat U, Ayaz A, Shrivastava D, Shah RA, Ganai NA. (2017) LncRNAs and immunity: watchdogs for host pathogen interactions. Biol Proced Online 19:3. [article]

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