The RNA modification N6-methyladenosine as a novel regulator of the immune system

Shulman, Ziv; Stern-Ginossar, Noam

doi:10.1038/s41590-020-0650-4

Cited by 316 publications

(291 citation statements)

References 143 publications

Supporting

Mentioning

288

Contrasting

Unclassified

Order By: Relevance

“…RNA interactome studies show a proteome-wide picture of this interaction that is formed in vivo [165][166][167][168][169]. Diverse modifications on mRNAs also contribute to posttranscriptional regulation of immune responses [170]. These events seem to be changed by inflammatory signals quantitatively and qualitatively.…”

Section: Resultsmentioning

confidence: 99%

RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms

Uehata

Takeuchi

2020

Cells

View full text Add to dashboard Cite

RNA acts as an immunostimulatory molecule in the innate immune system to activate nucleic acid sensors. It functions as an intermediate, conveying genetic information to control inflammatory responses. A key mechanism for RNA sensing is discriminating self from non-self nucleic acids to initiate antiviral responses reliably, including the expression of type I interferon (IFN) and IFN-stimulated genes. Another important aspect of the RNA-mediated inflammatory response is posttranscriptional regulation of gene expression, where RNA-binding proteins (RBPs) have essential roles in various RNA metabolisms, including splicing, nuclear export, modification, and translation and mRNA degradation. Recent evidence suggests that the control of mRNA stability is closely involved in signal transduction and orchestrates immune responses. In this study, we review the current understanding of how RNA is sensed by host RNA sensing machinery and discuss self/non-self-discrimination in innate immunity focusing on mammalian species. Finally, we discuss how posttranscriptional regulation by RBPs shape immune reactions.

show abstract

Section: Resultsmentioning

confidence: 99%

RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms

Uehata

Takeuchi

2020

Cells

View full text Add to dashboard Cite

show abstract

“…While m 6 A modification of endogenous RNAs impacts immune cell function and development in several contexts, many studies have also investigated how m 6 A modification of exogenous viral RNAs modulates the host immune response during infection [63]. The roles of m 6 A in the immune response have been summarized in depth in a recent review by Shulman and Stern-Ginossar [64]. Here, we will highlight a few relevant studies which offer a general overview of m 6 A function in immune regulation and how this might globally impact hematopoiesis.…”

Section: Rna Modification and Immune Functionmentioning

confidence: 99%

The Role of RNA Epigenetic Modification in Normal and Malignant Hematopoiesis

et al. 2020

View full text Add to dashboard Cite

Purpose of Review RNA epigenetic modifications have been identified as novel, dynamic regulators of gene expression, with important impacts on stem cell fate decisions. Here, we examine the functions of RNA modifications, with a focus on N 6methyladenosine (m 6 A), in hematopoietic stem cells under normal conditions and in malignancy. Recent Findings The m 6 A RNA modification is a critical regulator of hematopoiesis. Disruption of different elements of the m 6 A machinery can skew the balance of self-renewal and differentiation in normal hematopoietic stem cells. The m 6 A reader, writer, and eraser proteins are also overexpressed in myeloid leukemia, and disruption of their function impairs leukemogenesis. RNA m 6 A modification governs important aspects of immune system function, including immune cell development, immune signaling, and recognition of RNA as foreign or self. In hematopoietic stem cells, endogenously derived double-stranded RNA can form in the absence of m 6 A, inducing deleterious inflammatory pathways which compromise stem cell function. Summary The RNA modification m 6 A exerts a variety of functions in normal hematopoietic stem cells as well as leukemic cells. Pharmacologic modulation of different elements of the m 6 A machinery provides a promising avenue for ex vivo expansion of hematopoietic stem cells in the transplant setting, as well as for leukemia therapy. Keywords RNA modification. N 6-methyladenosine. m 6 A. Hematopoiesis. dsRNA This article is part of the Topical Collection on Classical Signalling Pathways * Radovan Vasic

show abstract

“…m 6 A modification regulates the metabolic processes of both messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs), which include structural stability, alternative splicing, translation efficacy, export, and decay (21)(22)(23)(24). The reciprocal effects of m 6 A methylation with mRNAs or ncRNAs are associated with a series of physiological and pathological biological behaviors such as stem cell differentiation, immunoregulation and carcinogenesis (25)(26)(27). There is mounting evidence that m 6 A dysregulation is critically involved in HCC occurrence and development.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of RNA N6-Methyladenosine in Hepatocellular Carcinoma: From the Perspectives of Etiology

Qian

Yin

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

N6-Methyladenosine (m 6 A) is the most common RNA internal modification in eukaryotic cells. Its regulatory effects at the post-transcriptional level on both messenger RNAs (mRNAs) and noncoding RNAs have been widely studied; these include alternative splicing, stability, translation efficiency, nucleus export, and degradation. m 6 A modification is implicated in a series of physiological and pathological activities, such as embryonic stem cell differentiation, immunoregulation, adipogenesis, and cancer development. Recently, the significance of m 6 A methylation has been identified in both viral hepatitis and non-alcohol fatty liver disease (NAFLD), which are major risk factors in the development of hepatocellular carcinoma (HCC). Given the high incidence and mortality rate of HCC worldwide, it is of great importance to elucidate the mechanisms underlying HCC initiation and progression. m 6 A as an emerging research focus has great potential to facilitate the understanding of HCC, particularly from an etiological perspective. Thus, in this review, we summarize recent progress in understanding m 6 A modification related to viral hepatitis, NAFLD, and HCC, including their mechanisms and clinical applications.

show abstract

The RNA modification N6-methyladenosine as a novel regulator of the immune system

Cited by 316 publications

References 143 publications

RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms

RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms

The Role of RNA Epigenetic Modification in Normal and Malignant Hematopoiesis

Mechanisms of RNA N6-Methyladenosine in Hepatocellular Carcinoma: From the Perspectives of Etiology

Contact Info

Product

Resources

About