The long noncoding RNA
            <i>Morrbid</i>
            regulates CD8 T cells in response to viral infection

Kotzin, Jonathan J.; Iseka, Fany; Wright, Jasmine M.; Basavappa, Megha; Clark, Megan L.; Ali, Mohammed-Alkhatim; Abdel-Hakeem, Mohamed S.; Robertson, Tanner F.; Mowel, Walter K.; Joannas, Leonel; Neal, Vanessa; Spencer, Sean P.; Syrett, Camille M.; Anguera, Montserrat C.; Williams, Adam; Wherry, E. John; Henao‐Mejia, Jorge

doi:10.1073/pnas.1819457116

Cited by 46 publications

(27 citation statements)

References 33 publications

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“…These ncRNAs can exhibit diverse roles in cellular and developmental processes but also in diseases such as cancer [11][12][13] , autoimmunity 14 , and cardiovascular disease 15,16 . A limited number of lncRNAs have been discovered and characterized as immune regulators including lncRNA-COX2 17 , THRIL 18 , lncRNA-EPS 19 , and Morrbid 20,21 . The molecular mechanisms that underlie the immunoregulatory functions for these RNAs are diverse.…”

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confidence: 99%

The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans

et al. 2020

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Long non-coding RNAs are important regulators of biological processes including immune responses. The immunoregulatory functions of lncRNAs have been revealed primarily in murine models with limited understanding of lncRNAs in human immune responses. Here, we identify lncRNA LUCAT1 which is upregulated in human myeloid cells stimulated with lipopolysaccharide and other innate immune stimuli. Targeted deletion of LUCAT1 in myeloid cells increases expression of type I interferon stimulated genes in response to LPS. By contrast, increased LUCAT1 expression results in a reduction of the inducible ISG response. In activated cells, LUCAT1 is enriched in the nucleus where it associates with chromatin. Further, LUCAT1 limits transcription of interferon stimulated genes by interacting with STAT1 in the nucleus. Together, our study highlights the role of the lncRNA LUCAT1 as a post-induction feedback regulator which functions to restrain the immune response in human cells.

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confidence: 99%

The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans

et al. 2020

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“…During the early stages of choriomeningitis virus infection, the transcription of the lncRNA-Morrbid is specifically induced by type I IFN stimulation and T cell receptor (TCR). As a response, the Morrbid and its locus govern the survival, proliferation and effector function of CD8 + T cell through controlling the pro-apoptotic factor, Bcl2l11, and activating the PI3K/Akt pathway [ 170 ]. LncRNA-CD160 eliminates the immune activity of CD8 + T cells via epigenetic mechanisms in hepatitis B virus infection.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA: a dazzling dancer in tumor immune microenvironment

Zhang

Liu

Liao

2020

J Exp Clin Cancer Res

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Long noncoding RNAs (lncRNAs) are a class of endogenous, non-protein coding RNAs that are highly linked to various cellular functions and pathological process. Emerging evidence indicates that lncRNAs participate in crosstalk between tumor and stroma, and reprogramming of tumor immune microenvironment (TIME). TIME possesses distinct populations of myeloid cells and lymphocytes to influence the immune escape of cancer, the response to immunotherapy, and the survival of patients. However, hitherto, a comprehensive review aiming at relationship between lncRNAs and TIME is missing. In this review, we focus on the functional roles and molecular mechanisms of lncRNAs within the TIME. Furthermore, we discussed the potential immunotherapeutic strategies based on lncRNAs and their limitations.

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“…The present study is focused on the uncovering of moonlight functions of murine Morrbid lncRNA in hepatocytes. Previously, Kotzin et al demonstrated that Morrbid lncRNA plays an important role in the proliferation and survival of immune cells in mice [ 16 , 17 , 18 ]. Morrbid knockout mice have reduced levels of eosinophils, neutrophils and Ly6C hi classical monocytes in the peripheral blood and tissues [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…In preleukemic Hematopoietic Stem and Progenitor Cells (HSPC) depleted of the Tet2 gene, Morrbid is a key component of the signaling pathway promoting the enhanced survival and reduced apoptosis of Tet2 -KO cells [ 18 ]. Despite the apparent inhibitory role of Morrbid in the regulation of Bcl2l11 in myeloid cells and HSPC, in CD8+ T cells, Morrbid was shown to be essential for the upregulation of Bcl2l11 expression in response to Lymphocytic Choriomeningitis Virus (LCMV) infection signaling [ 17 ]. In spite of a thorough characterization of Morrbid lncRNA in myeloid cells, nothing is known about its functions in other cells and tissues.…”

Section: Introductionmentioning

confidence: 99%

Murine Long Noncoding RNA Morrbid Contributes in the Regulation of NRAS Splicing in Hepatocytes In Vitro

Fefilova

Melnikov

Prikazchikova

et al. 2020

IJMS

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The coupling of alternative splicing with the nonsense-mediated decay (NMD) pathway maintains quality control of the transcriptome in eukaryotes by eliminating transcripts with premature termination codons (PTC) and fine-tunes gene expression. Long noncoding RNA (lncRNA) can regulate multiple cellular processes, including alternative splicing. Previously, murine Morrbid (myeloid RNA repressor of Bcl2l11 induced death) lncRNA was described as a locus-specific controller of the lifespan of short-living myeloid cells via transcription regulation of the apoptosis-related Bcl2l11 protein. Here, we report that murine Morrbid lncRNA in hepatocytes participates in the regulation of proto-oncogene NRAS (neuroblastoma RAS viral oncogene homolog) splicing, including the formation of the isoform with PTC. We observed a significant increase of the NRAS isoform with PTC in hepatocytes with depleted Morrbid lncRNA. We demonstrated that the NRAS isoform with PTC is degraded via the NMD pathway. This transcript is presented almost only in the nucleus and has a half-life ~four times lower than other NRAS transcripts. Additionally, in UPF1 knockdown hepatocytes (the key NMD factor), we observed a significant increase of the NRAS isoform with PTC. By a modified capture hybridization (CHART) analysis of the protein targets, we uncovered interactions of Morrbid lncRNA with the SFPQ (splicing factor proline and glutamine rich)-NONO (non-POU domain-containing octamer-binding protein) splicing complex. Finally, we propose the regulation mechanism of NRAS splicing in murine hepatocytes by alternative splicing coupled with the NMD pathway with the input of Morrbid lncRNA.

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The long noncoding RNA Morrbid regulates CD8 T cells in response to viral infection

Cited by 46 publications

References 33 publications

The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans

The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans

Long noncoding RNA: a dazzling dancer in tumor immune microenvironment

Murine Long Noncoding RNA Morrbid Contributes in the Regulation of NRAS Splicing in Hepatocytes In Vitro

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