Long Non-Coding RNAs and Immunity

Editorial

09 October 2019

Editorial: Long Non-coding RNAs and Immunity

Grace J. Kwon

Jorge Henao-Mejia

and

Adam Williams

3,470 views

5 citations

Editors

Adam Williams

Feinberg School of Medicine, Northwestern University

Jorge Henao-Mejia

University of Pennsylvania

Impact

Schematic representation of the function of inflammation associated SNP harboring lncRNAs. (A) Lnc13 harbors a CeD associated SNP that changes the secondary structure of the lncRNA modifying its binding with the proteins hnRNPD and HDAC1 and regulating the expression of disease related inflammatory genes. (B) LINC00305 interacts with the transmembrane protein LIMR facilitating the binding of this protein to AHRR that in turn induces the translocation of the latter to the nucleus inducing NFκB and subsequent inflammatory gene expression. Atherosclerosis patients present higher levels of this lincRNA which could be influenced by a SNP located in the promoter region of LINC00305. (C) IFNG-AS1 is closely located to IFNG gene. Activation of its transcription leads to induction of IFNG by WDR5 mediated H3K4me3 methylation. IBD patients present higher levels of IFNG-AS1 that could be related to a disease associated SNP located in the enhancer region of the lncRNA. (D) Suggested SNP related splicing model for ANRIL mediated inflammation regulation. The inflammation associated allele will affect ANRIL splicing generating a linear ANRIL that will interact with a member of the PRC1 complex mediating an epigenetic transcriptional repression of the INK4a gene via H3K27me3.

Review

08 March 2019

Disease-Associated SNPs in Inflammation-Related lncRNAs

Ainara Castellanos-Rubio

and

Sankar Ghosh

Immune-mediated diseases, such as celiac disease, type 1 diabetes or multiple sclerosis, are a clinically heterogeneous group of diseases that share many key genetic triggers. Although the pathogenic mechanisms responsible for the development of immune mediated disorders is not totally understood, high-throughput genomic studies, such as GWAS and Immunochip, performed in the past few years have provided intriguing hints about underlying mechanisms and pathways that lead to disease. More than a hundred gene variants associated with disease susceptibility have been identified through such studies, but the progress toward understanding the underlying mechanisms has been slow. The majority of the identified risk variants are located in non-coding regions of the genome making it difficult to assign a molecular function to the SNPs. However, recent studies have revealed that many of the non-coding regions bearing disease-associated SNPs generate long non-coding RNAs (lncRNAs). LncRNAs have been implicated in several inflammatory diseases, and many of them have been shown to function as regulators of gene expression. Many of the disease associated SNPs located in lncRNAs modify their secondary structure, or influence expression levels, thereby affecting their regulatory function, hence contributing to the development of disease.

15,735 views

83 citations

Review

25 January 2019

The Opening of Pandora's Box: An Emerging Role of Long Noncoding RNA in Viral Infections

Pin Wang

lncRNAs influence immune defense responses through directly interacting with sensors, adaptors, effecters, and transcriptional factors. Light blue represents sensors, cyan represents effecters, light purple represents signaling adaptors, and light brown represents transcriptional factors.

Emerging evidence has proved that long noncoding RNAs (lncRNAs) participate in various physiological and pathological processes. Recent evidence has demonstrated that lncRNAs are crucial regulators of virus infections and antiviral immune responses. Upon viral infections, significant changes take place at the transcriptional level and the majority of the expression modifications occur in lncRNAs from both the host and viral genomes with dynamic regulatory courses. These lncRNAs exert diverse effects. Some are antiviral either through directly inhibiting viral infections or through stimulating antiviral immune responses, while others are pro-viral through directly promoting virus replication or through influencing cellular status, such as suppressing antiviral mechanisms. Consequently, these dynamic regulations lead to disparate pathophysiological outcomes and clinical manifestations. This review will focus on the roles of lncRNAs in viral infection and antiviral responses, summarize expression patterns of both host- and virally derived lncRNAs, describe their acting stages and modes of action, discuss challenges and novel concepts, and propose solutions and perspectives. Research into lncRNA will help identify novel viral infection-related regulators and design preventative and therapeutic strategies against virus-related diseases and immune disorders.

10,381 views

53 citations

Cataloging of up-regulated lncRNA transcripts based on chromatin signatures. (A) cataloging of up-regulated lncRNA transcripts based on their orientation with respect to nearby PCGs; (B) Representative plot showing log2 ratio of chromatin signatures H3K4Me1 and H3K4Me3 (after normalization with input) around 4 window of transcription start site (TSS) of lncRNAs; (C) Average normalized RPKM (reads per kilobase million) values of H3K4Me1 in elncRNAs and plncRNAs; (D) Average normalized RPKM (reads per kilobase million) values of H3K4Me3 in elncRNAs and plncRNAs; (E) Distribution of distances of elncRNAs and plncRNAs from their respective nearby genes; and (F) Correlation between fold changes of elncRNAs and plncRNAs and their closest protein coding genes (PCGs), respectively. The linear regression curves of the best fit are shown as dotted line for elncRNA and solid line for plncRNA. ***P ≤ 0.001.

Original Research

09 January 2019

Enhancer Associated Long Non-coding RNA Transcription and Gene Regulation in Experimental Models of Rickettsial Infection

Imran H. Chowdhury

, 4 more and

Sanjeev K. Sahni

6,630 views

14 citations

Review

18 December 2018

Circular RNAs and Their Emerging Roles in Immune Regulation

Lan Yang

, 1 more and

Yufeng Zhou

CircRNAs in immune responses. Exogenous circRNAs can activate the RIG-1 cellular immune response pathway to suppress viral replication. The immune factor NF90/NF110 can promote circRNA formation by stabilizing the intron complementary sequence. Under viral infection, NF90/NF110 is exported from the nucleus to the cytoplasm to inhibit virus replication. Meanwhile, circRNA expression in the nucleus is decreased. Thus, endogenous circRNAs can be used as “molecular indicators” of antiviral proteins to prompt antiviral immune responses. circRNAs can also function as “microRNA sponges” to increase expression of target proteins involved in antiviral responses or tumor immunity, such as PD-L1. mcircRasGEF1B can help to protect cells from bacterial infection by enhancing the stability of mature ICAM-1 mRNA. In addition, circRNAs can be involved in immune responses by interacting with proteins or their host genes.

Circular ribonucleic acid (RNA) molecules (circRNAs) are covalently closed loop RNA molecules with no 5′ end caps or 3′ poly (A) tails, which are generated by back-splicing. Originally, circRNAs were considered to be byproducts of aberrant splicing. However, in recent years, development of high-throughput sequencing has led to gradual recognition of functional circRNAs, and increasing numbers of studies have elucidated their roles in cancer, neurologic diseases, and cardiovascular disorders. Nevertheless, studies of the functions of circRNAs in the immune system are relatively scarce. In this review, we detail relevant research on the biogenesis and classification of circRNAs, describe their functional mechanisms and approaches to their investigation, and summarize recent studies of circRNA function in the immune system.

10,890 views

86 citations