N6-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I

Lu, Mijia; Zhang, Zijie; Xue, Miaoge; Zhao, Boxuan Simen; Harder, Olivia; Li, Anzhong; Liang, Xueya; Gao, Thomas Z.; Xu, Yunsheng; Zhou, Jiyong; Feng, Zongdi; Niewiesk, Stefan; Peeples, Mark E.; He, Chuan; Lǐ, Jiànróng

doi:10.1038/s41564-019-0653-9

Cited by 205 publications

(223 citation statements)

References 61 publications

(71 reference statements)

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“…However, emerging evidence also suggests that METTL3 plays vital roles in other biological processes, such as angiogenesis [58] and metabolism dysregulation [58,101]. A recent publication showed that m 6 A modification of viral RNA enables the virus to avoid detection by innate immunity [143]; thus, there is a possibility that METTL3 might also mediate immune escape in cancers. Further studies are warranted to fully uncover the roles and mechanisms of METTL3 in affecting every hallmark of cancer.…”

Section: Discussionmentioning

confidence: 99%

Roles of METTL3 in cancer: mechanisms and therapeutic targeting

et al. 2020

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N 6-methyladenosine (m 6 A) is the most abundant mRNA modification and is catalyzed by the methyltransferase complex, in which methyltransferase-like 3 (METTL3) is the sole catalytic subunit. Accumulating evidence in recent years reveals that METTL3 plays key roles in a variety of cancer types, either dependent or independent on its m 6 A RNA methyltransferase activity. While the roles of m 6 A modifications in cancer have been extensively reviewed elsewhere, the critical functions of METTL3 in various types of cancer, as well as the potential targeting of METTL3 as cancer treatment, have not yet been highlighted. Here we summarize our current understanding both on the oncogenic and tumor-suppressive functions of METTL3, as well as the underlying molecular mechanisms. The welldocumented protein structure of the METTL3/METTL14 heterodimer provides the basis for potential therapeutic targeting, which is also discussed in this review.

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Section: Discussionmentioning

confidence: 99%

Roles of METTL3 in cancer: mechanisms and therapeutic targeting

et al. 2020

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“…Therefore, increased expression levels of viral proteins were observed in A549 cells experimentally infected with HMPV, along with the overexpression of METTL3 and METTL14 and YTHDF1-3. Interestingly, infection with intact (m 6 A-unmethylated) HMPV activates the expression levels of RIG-I, followed by the activation of IFN-I and NF-κB pathways [126]. Furthermore, another study showed that IFN-β is significantly activated in cotton rats infected by intact HMPV, showing low virulence and significant induction of virus-neutralizing antibodies at two weeks post-infection [126].…”

Section: The Relationship Between M 6 a Methylation And Viral Infectimentioning

confidence: 99%

Critical Roles of N6-Methyladenosine (m6A) in Cancer and Virus Infection

et al. 2020

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Studies have shown that epigenetic abnormalities are involved in various diseases, including cancer. In particular, in order to realize precision medicine, the integrated analysis of genetics and epigenetics is considered to be important; detailed epigenetic analysis in the medical field has been becoming increasingly important. In the epigenetics analysis, DNA methylation and histone modification analyses have been actively studied for a long time, and many important findings were accumulated. On the other hand, recently, attention has also been focused on RNA modification in the field of epigenetics; now it is known that RNA modification is associated with various biological functions, such as regulation of gene expression. Among RNA modifications, functional analysis of N6-methyladenosine (m6A), the most abundant RNA modification found from humans to plants is actively progressing, and it has also been known that m6A abnormality is involved in cancer and other diseases. Importantly, recent studies have shown that m6A is related to viral infections. Considering the current world situation under threat of viral infections, it is important to deepen knowledge of RNA modification from the viewpoint of viral diseases. Hence, in this review, we have summarized the recent findings regarding the roles of RNA modifications in biological functions, cancer biology, and virus infection, particularly focusing on m6A in mRNA.

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“…Using human metapneumovirus (HMPV) as a model, Lu et al show that depletion of m 6 A from viral RNA facilitates their detection by PRRs. Loss of m 6 A consequently enhances HMPV immunogenicity and attenuates infectivity [65]. In theory, manipulation of m 6 A could therefore facilitate adjuvant or vaccine development.…”

Section: Rna Modification and Immune Functionmentioning

confidence: 99%

The Role of RNA Epigenetic Modification in Normal and Malignant Hematopoiesis

et al. 2020

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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

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N6-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I

Cited by 205 publications

References 61 publications

Roles of METTL3 in cancer: mechanisms and therapeutic targeting

Roles of METTL3 in cancer: mechanisms and therapeutic targeting

Critical Roles of N6-Methyladenosine (m6A) in Cancer and Virus Infection

The Role of RNA Epigenetic Modification in Normal and Malignant Hematopoiesis

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