Long noncoding RNA CHROMR regulates antiviral immunity in humans

Abstract

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their contribution to immune regulation in humans remains poorly understood. Here, we report that the primate-specific lncRNA CHROMR is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. CHROMR depletion in human macrophages reduces histone acetylation at regulatory regions of ISG loci and attenuates ISG expression in response to microbial stimuli. Mechanistically, we show that CHROMR sequesters the interferon regulatory factor (IRF)-2-dependent transcriptional corepressor IRF2BP2, thereby licensing IRF-dependent signaling and transcription of the ISG network. Consequently, CHROMR expression is essential to restrict viral infection of macrophages. Our findings identify CHROMR as a key arbitrator of antiviral innate immune signaling in humans.

Interactomics: Dozens of Viruses, Co-evolving With Humans, Including the Influenza A Virus, may Actively Distort Human Aging

“…Data sources (DEG data set: articles or data set identifier) are numbered and visually delimited by an alternance of light-gray/dark-gray backgrounds, with some sources providing several samples or time points ( supplementary table S10, Supplementary Material online). Samples sources are: (1) Alberts et al (2022) ; (2) Park et al (2022) ; (3) van Solingen et al (2022) ; (4) Chandrashekar et al (2021) ; (5) Chow et al (2021) ; (6) Blanco-Melo et al (2020) ; (7) Deshiere et al (2017) ; (8) Golumbeanu et al (2019) ; (9) van der Heijden et al (2021) ; (10) Bauby et al (2021) ; (11) GSE53993; (12) Coelho et al (2021) ; (13, 14) Devadas et al (2016) ; (15) Bell et al (2022) ; (16) GSE186908; (17) GSE192528; (18) Thompson et al (2020) ; (19, 63–65) Tsalik et al (2021) ; (20, 28, 62) Dissanayake et al (2020) ; . (21) Zhuravlev et al (2020) ; (22) GSE97672; (23, 27) GSE89008; (24) GSE82232; (25) GSE101760; (26) GSE97672; (29) Sheng et al (2020) ; (30) Hong et al (2021) ; (31) Mrozek-Gorska et al (2019) ; (32) Wang et al (2019) ; (33) Yanagi et al (2021) ; (34) GSE84897; (35) Tso et al (2018) ; (36) Journo et al (2018) ; (37) GSE79032; (38) Seelbinder et al (2020) ; (39) Oberstein and Shenk (2017) ; (40–42) Sen et al (2020) ; (43) Zhang et al (2016) ; (44, 49) Jagya et al (2014) ; (45) Yuan et al (2021) ; (46) GSE194179; (47) Zai et al (2022) ; (48) Winer et al (2020) ; (50) Montanari et al (2022) ; (51) Tegtmeyer et al (2021) ; (52) Hojka-Osinska et al (2017) ; (53) Li et al (2020) ; (54) GSE84346; (55) Hu et al (2016) ; (56, 59, 60) Kaczkowski et al (2012) ; (57)…”

Antisense lncRNA CHROMR is linked to glioma patient survival

“…Though it could be expected that lncRNA overlapping sense mRNA would modulate the levels of overlapped gene mRNA, such an effect could not be observed regarding lncRNA CHROMR and protein coding PRKRA . Indeed, it has been shown that CHROMR shows a weak interaction with the PRKRA genomic locus and that CHROMR expression does not impact the expression of the PRKRA gene ( van Solingen et al, 2022 ) at least in the context of macrophages. However, lncRNA are known for their ability to modulate gene activity without impacting levels of mRNA, so it is not yet conclusive that CHROMR does not interact with PRKRA .…”

“…However, lncRNA are known for their ability to modulate gene activity without impacting levels of mRNA, so it is not yet conclusive that CHROMR does not interact with PRKRA . Interestingly, CHROMR has been shown to have histone binding affinity in macrophages ( van Solingen et al, 2022 ), which could still be an avenue for PRKRA regulation, without binding to PRKRA mRNA. It is also known that CHROMR can act as a sponge for various miRNAs ( Hennessy et al, 2019 ; Wang et al, 2022 ), but it would be difficult to attribute miRNA sponging to observed effects on glioma.…”

“…CHROMR has also been implicated in elevated risk for stomach adenocarcinoma ( Luo et al, 2022 ), lung adenocarcinoma ( Bai et al, 2022 ), increased resistance to chemotherapy in Lymphoma ( Wang et al, 2022 ), but also in antiviral response to Influenza and COVID-19 infections ( van Solingen et al, 2022 ) and autoimmune disease, such as multiple sclerosis ( Teimuri et al, 2018 ). CHROMR expression is different when comparing lymphoid cancer (high) with myeloid cancer (low) cell lines ( Yang et al, 2022 ).…”

“…AC009948.5, CHROME and PRKRA-AS1 ) is found to be involved in controlling cholesterol homeostasis in humans, by sponging inhibitory micro RNAs (miRNAs) miR-27b, miR-33a, miR-33b and miR-128 ( Hennessy et al, 2019 ). In addition, recent data, has linked CHROMR with several types of cancer ( Bai et al, 2022 ; Luo et al, 2022 ; Wang et al, 2022 ), antiviral response ( van Solingen et al, 2022 ) and autoimmune disease ( Teimuri et al, 2018 ). Based on the location of CHROMR in the Human genome with respect to the protein-coding gene, in GENECODE 7 annotation ( Derrien et al, 2012 ) it is categorized as biotype “non-coding natural antisense transcript”, as the 3′ end of CHROMR overlaps with the 3′ end of its paired sense gene PRKRA.…”