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Article ; Online: CircYthdc2 generates polypeptides through two translation strategies to facilitate virus escape.

Zheng, Weiwei / Wang, Linchao / Geng, Shang / Xu, Tianjun

Cellular and molecular life sciences : CMLS

2024 Volume 81, Issue 1, Page(s) 91

Abstract: It is known that about 10 circular RNAs (circRNAs) can encode functional polypeptides in higher mammals. However, it is not clear whether the functional polypeptides that can be translated by circRNAs are only the products of the evolution of higher ... ...

Abstract	It is known that about 10 circular RNAs (circRNAs) can encode functional polypeptides in higher mammals. However, it is not clear whether the functional polypeptides that can be translated by circRNAs are only the products of the evolution of higher animals, or also widely exist in other lower organisms. In addition, it is also unclear whether the two ways of translating polypeptides using IRES and m
MeSH term(s)	Animals ; Humans ; RNA, Circular/genetics ; Peptides/genetics ; Mammals/genetics
Chemical Substances	RNA, Circular ; Peptides
Language	English
Publishing date	2024-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-024-05148-9
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Article ; Online: METTL3-Mediated m6A Modification of TRIF and MyD88 mRNAs Suppresses Innate Immunity in Teleost Fish, Miichthys miiuy.

Geng, Shang / Zheng, Weiwei / Zhao, Yan / Xu, Tianjun

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 211, Issue 1, Page(s) 130–139

Abstract: Methyltransferase (METTL3), the most important N6-methyladenosine (m6A) writer, plays a vital role in regulating immune-related signaling pathways. However, the underlying mechanism of METTL3 action remains largely unknown, especially in lower ... ...

Abstract	Methyltransferase (METTL3), the most important N6-methyladenosine (m6A) writer, plays a vital role in regulating immune-related signaling pathways. However, the underlying mechanism of METTL3 action remains largely unknown, especially in lower vertebrates. The results of this study show that METTL3 inhibits innate immune response and promotes the infection of miiuy croaker, Miichthys miiuy, by Siniperca chuatsi rhabdovirus and Vibrio anguillarum. Significantly, the function of METTL3 in inhibiting immunity depends on its methylase activity. Mechanistically, METTL3 increases the methylation level of trif and myd88 mRNA, rendering them sensitive to degradation by the YTHDF2/3 reader proteins. By contrast, we found that the YTHDF1 reader protein promotes the translation of myd88 mRNA. In summary, these results indicate that METTL3-mediated m6A modification of trif and myd88 mRNAs suppresses innate immunity by inhibiting the TLR pathway, unveiling a molecular mechanism by which RNA methylation controls innate immunity to pathogens in the teleost fish.
MeSH term(s)	Animals ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Myeloid Differentiation Factor 88/genetics ; Myeloid Differentiation Factor 88/metabolism ; Methyltransferases/genetics ; Methyltransferases/metabolism ; Adaptor Proteins, Signal Transducing/metabolism ; Perciformes/genetics ; Immunity, Innate ; Adaptor Proteins, Vesicular Transport/genetics ; Adaptor Proteins, Vesicular Transport/metabolism
Chemical Substances	RNA, Messenger ; Myeloid Differentiation Factor 88 ; Methyltransferases (EC 2.1.1.-) ; Adaptor Proteins, Signal Transducing ; Adaptor Proteins, Vesicular Transport
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2300033
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Article ; Online: FTO promotes innate immunity by controlling NOD1 expression via m

Geng, Shang / Zheng, Weiwei / Zhao, Yan / Xu, Tianjun

iScience

2022 Volume 25, Issue 12, Page(s) 105646

Abstract: N6-methyladenosine ( ... ...

Abstract	N6-methyladenosine (m
Language	English
Publishing date	2022-11-22
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.105646
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Article ; Online: Genomic organization, evolution and functional characterization of embryonic lethal abnormal vision like protein 1 (ELAVL1) in miiuy croaker (Miichthys miiuy)

Wang, Wansu / Luo, Qiang / Zhao, Yan / Geng, Shang / Xu, Tianjun / Sun, Yuena

Developmental and Comparative Immunology. 2023 Feb. 08, p.104659-

2023 , Page(s) 104659–

Abstract: Embryonic lethal vision-like protein 1 (ELAVL1), an AU-rich elements (AREs) binding protein involved in the regulation of inflammatory transcript stability, which has not been reported in fish. In this study, we identified the ELAVL1 gene in Miichthys ... ...

Abstract	Embryonic lethal vision-like protein 1 (ELAVL1), an AU-rich elements (AREs) binding protein involved in the regulation of inflammatory transcript stability, which has not been reported in fish. In this study, we identified the ELAVL1 gene in Miichthys miiuy (mmiELAVL1), and then analyzed its structure and evolution, furthermore described its expression pattern in miiuy croaker. The results showed that mmiELAVL1 and other vertebrate ELAVL1 genes all have three highly conserved RNA recognition motif (RRM) protein domains, and the structure and protein structure are evolutionarily conserved, indicating that their functions may also conservative. In healthy miiuy croaker, mmiELAVL1 was commonly expressed in the tested tissues, and mmiELAVL1 is mainly localized in the nucleus of kidney cells. In addition, mmiELAVL1 responds to poly(I:C) and SCRV stimulation and promotes antiviral genes, indicating its active role in immune process. In summary, this study will facilitate future studies on the role and underlying mechanisms of ELAVL1 in fish immune responses.
Keywords	Miichthys miiuy ; RNA ; evolution ; fish ; genes ; immunology ; kidneys ; nucleotide sequences ; protein structure ; vision ; ELAVL1 ; Structure ; Expression ; Miiuy croaker
Language	English
Dates of publication	2023-0208
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2023.104659
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Article ; Online: METTL16, an evolutionarily conserved m6A methyltransferase member, inhibits the antiviral immune response of miiuy croaker (Miichthys miiuy)

Zhao, Yan / Luo, Qiang / Wang, Wansu / Geng, Shang / Sun, Yuena / Xu, Tianjun

Developmental and Comparative Immunology. 2023 Aug., v. 145 p.104713-

2023

Abstract: Methyltransferase like-16 (METTL16) is an m6A RNA methylation transferase that is known to methylate U6 snRNA and pre-mRNA of S-adenosylmethionine synthase but has been poorly studied in fish. In this study, METTL16 was identified in miiuy croaker ( ... ...

Abstract	Methyltransferase like-16 (METTL16) is an m6A RNA methylation transferase that is known to methylate U6 snRNA and pre-mRNA of S-adenosylmethionine synthase but has been poorly studied in fish. In this study, METTL16 was identified in miiuy croaker (Miichthys miiuy). We first performed bioinformatics analysis of the miiuy croaker METTL16 (mmiMETTL16). MmiMETTL16 and other vertebrates METTL16 have a relatively conserved MTD structural domain and gene structure, suggesting that their methylase activity may also be conservative. In healthy miiuy croaker, mmiMETTL16 was commonly expressed in the tested tissues. Expression of mmiMETTL16 in kidney, liver, and spleen tissues was significantly increased after poly(I:C) stimulation. Consistently, mmiMETTL16 was sensitive to poly(I:C) stimulation in miiuy croaker kidney cell (MKC), suggesting that METTL16 might participate in antiviral immunity. For further functional experiments, immunofluorescence of mmiMETTL16 presents in the nucleus in kidney cells. In addition, the overexpression of mmiMETTL16 could significantly increase the overall m6A level of MKC cells, which shows that the function of METTL16 as methyltransferase is conservative in miiuy croaker. Last, mmiMETTL16 can inhibit the expression of TNF-α, IFN-1, Mx1, and ISG15, suggesting that mmiMETTL16 can suppress the immune response caused by viral stimulation. In summary, studies on mmiMETTL16 will contribute to future studies on the role of METTL16 and potential mechanisms of the m6A regulation network in the teleost immune system.
Keywords	Miichthys miiuy ; RNA ; bioinformatics ; fish ; fluorescent antibody technique ; genes ; immune response ; kidneys ; liver ; methionine adenosyltransferase ; methylation ; methyltransferases ; spleen ; METTL16 ; Structure ; Evolution
Language	English
Dates of publication	2023-08
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2023.104713
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Article: Genome-wide identification and analysis of chemokine receptor superfamily in miiuy croaker, Miichthys miiuy

Geng, Shang / Xu, Tianjun / Sun, Yuena

Fish & shellfish immunology. 2021 Nov., v. 118

2021

Abstract: The chemokine receptor (ChemR) superfamily, which is divided into 4 subfamilies (CXCR, CCR, XCR, and CX3CR), is the main receptors of chemokines in innate immune responses. In the current study, we have identified 27 ChemRs in miiuy croaker: 13 CCR genes, ...

Abstract	The chemokine receptor (ChemR) superfamily, which is divided into 4 subfamilies (CXCR, CCR, XCR, and CX3CR), is the main receptors of chemokines in innate immune responses. In the current study, we have identified 27 ChemRs in miiuy croaker: 13 CCR genes, 11 CXCR genes, and 3 XCR genes. Multiple characteristics of these genes, including phylogeny, gene structures, conserved motifs, chromosome locations, evolutionary mechanism, and expression levels upon the bacterial challenge were analyzed. Gene structure and location analysis showed that all ChemR genes contain fewer introns (≤4) and they are unevenly distributed on the 12 chromosomes. And the XCR subfamily of miiuy croaker don't have the DRY motif of ChemR. Phylogenetic and synteny analysis showed that these genes experienced tandem and segmental duplication event in several species, and tandem duplication might be the main expansion way in miiuy croaker. The major ChemRs of each orthologous group in vertebrates were selected for molecular evolution analysis, the results of which indicated that compared with vertebrates, ChemRs of teleost fishes may have a relatively high evolutionary dynamic. In addition, a total of 21 positively selected codons were detected in vertebrate ChemRs under Model 8. RNA-Seq analysis and qRT-PCR verification demonstrated that CXCR3.2, CXCR5, and XCR1 genes were up-regulated significantly upon the Vibrio harveyi infection. These results provide valuable information for investigating the evolutionary relationships of chemokine receptor superfamily in miiuy croaker and laid the basis for further functional analysis.
Keywords	Miichthys miiuy ; Vibrio harveyi ; chemokines ; chromosomes ; codons ; fish ; introns ; phylogeny ; sequence analysis ; shellfish
Language	English
Dates of publication	2021-11
Size	p. 343-353.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1067738-0
ISSN	1095-9947 ; 1050-4648
ISSN (online)	1095-9947
ISSN	1050-4648
DOI	10.1016/j.fsi.2021.09.017
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Article ; Online: CircMIB2 therapy can effectively treat pathogenic infection by encoding a novel protein.

Zheng, Weiwei / Wang, Linchao / Geng, Shang / Yang, Liyuan / Lv, Xing / Xin, Shiying / Xu, Tianjun

Cell death & disease

2023 Volume 14, Issue 8, Page(s) 578

Abstract: The mRNA therapy is widely used in the treatment of diseases due to its efficient characteristics, and the COVID-19 vaccine is the application of mRNA therapy. However, due to the instability of mRNA, mRNA vaccines often need lots of modifications to ... ...

Abstract	The mRNA therapy is widely used in the treatment of diseases due to its efficient characteristics, and the COVID-19 vaccine is the application of mRNA therapy. However, due to the instability of mRNA, mRNA vaccines often need lots of modifications to ensure its stability. Recent research shows that circRNA with stable RNA structure can encode protein, which provides a new direction for mRNA therapy. Here, we discovered a novel circRNA (circMIB2) derived from E3 ubiquitin-protein ligase MIB2 (MIB2) gene in lower vertebrate fish, which can translate into a 134 amino acid protein (MIB2-134aa) through m
MeSH term(s)	Animals ; Humans ; COVID-19 Vaccines ; RNA, Circular/genetics ; TNF Receptor-Associated Factor 6 ; Zebrafish/genetics ; COVID-19 ; RNA, Messenger/genetics ; Ubiquitin-Protein Ligases/genetics
Chemical Substances	COVID-19 Vaccines ; RNA, Circular ; TNF Receptor-Associated Factor 6 ; RNA, Messenger ; MIB2 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2023-08-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-023-06105-3
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Article ; Online: circCBL and its host gene

Lv, Xing / Zheng, Weiwei / Geng, Shang / Cui, Yanqiu / Tao, Yaqi / Xu, Tianjun

Journal of virology

2023 Volume 97, Issue 10, Page(s) e0104623

Abstract: Importance: Increasing evidence indicates that circular RNAs exert crucial functions in regulating gene expression in mammals. However, the function of circRNAs in lower vertebrates still needs further exploration. Our research results demonstrated that ...

Abstract	Importance: Increasing evidence indicates that circular RNAs exert crucial functions in regulating gene expression in mammals. However, the function of circRNAs in lower vertebrates still needs further exploration. Our research results demonstrated that circRNA, namely circCBL, is involved in modulating antiviral and antibacterial immune responses in lower vertebrates. In addition, our study also found that circCBL can serve as a competing endogenous RNA to facilitate MITA expression, thereby modulating MITA-mediated innate immunity. Further research has proved that the host gene
MeSH term(s)	Animals ; Immunity, Innate ; MicroRNAs/genetics ; MicroRNAs/metabolism ; RNA, Circular/genetics ; RNA, Messenger/genetics ; Fishes/genetics ; Fishes/immunology
Chemical Substances	MicroRNAs ; RNA, Circular ; RNA, Messenger
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01046-23
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Article ; Online: Cytokine Receptor-Like Factor 3 Negatively Regulates Antiviral Immunity by Promoting the Degradation of TBK1 in Teleost Fish.

Yan, Xiaolong / Zheng, Weiwei / Geng, Shang / Zhou, Ming / Xu, Tianjun

Journal of virology

2022 Volume 97, Issue 1, Page(s) e0179222

Abstract: The cytokine receptor-like factor 3 (Crlf3) belongs to the orphan class I cytokine receptors and is identified as a neuroprotective erythropoietin receptor. In previous studies of Crlf3, few focused on its role in innate immunity. Therefore, this study ... ...

Abstract	The cytokine receptor-like factor 3 (Crlf3) belongs to the orphan class I cytokine receptors and is identified as a neuroprotective erythropoietin receptor. In previous studies of Crlf3, few focused on its role in innate immunity. Therefore, this study explored the regulatory role of Crlf3 in innate immunity. TANK-binding kinase 1 (TBK1) is a vital adaptor protein for the activation of the RLRs-MVAS-IRF3 antiviral signaling axis; thus, its expression and activity must be tightly regulated to maintain immune homeostasis and avoid undesirable effects. Here, we report that Crlf3 is a negative regulator of type I interferon production. The expression of Crlf3 is induced by poly(I·C) or Siniperca chuatsi rhabdovirus (SCRV) treatment. Silencing of Crlf3 enhanced poly(I·C)- and SCRV-induced type I interferon production, whereas overexpression of Crlf3 suppressed type I interferon production. Mechanistically, Crlf3 interacted with TBK1 via its N domain and then inhibited type I interferon production by promoting TBK1 proteasomal degradation through K48-linked polyubiquitination. Our study shows that Crlf3 is a key factor for viral escape from innate antiviral immunity in fish and provides a new perspective on mammalian resistance to viral invasion.
MeSH term(s)	Animals ; Immunity, Innate ; Phosphorylation ; Receptors, Cytokine/immunology ; Signal Transduction ; Fishes/immunology ; Fishes/virology ; Protein Serine-Threonine Kinases/metabolism ; Fish Proteins/metabolism ; Rhabdoviridae ; Rhabdoviridae Infections/immunology ; Rhabdoviridae Infections/veterinary ; Interferon Type I/immunology
Chemical Substances	Receptors, Cytokine ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Fish Proteins ; Interferon Type I
Language	English
Publishing date	2022-12-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01792-22
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Article ; Online: The m6A Reader YTHDF2 Modulates Antiviral and Antibacterial Activity by Suppressing METTL3 Methylation-Modified STING in Fish.

Geng, Shang / Zheng, Weiwei / Wang, Wansu / Lv, Xing / Xin, Shiying / Xu, Tianjun

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 210, Issue 5, Page(s) 653–667

Abstract: At present, N6-methyladenosine (m6A) modification has been proven to participate in a wide range of gene expression regulation, such as stability, translation, splicing, and output, among others, which has attracted much attention. Unlike mammals, ... ...

Abstract	At present, N6-methyladenosine (m6A) modification has been proven to participate in a wide range of gene expression regulation, such as stability, translation, splicing, and output, among others, which has attracted much attention. Unlike mammals, however, the role of m6A in innate immunity of lower invertebrates has not yet been studied. In this study, we found that the total m6A level of Miichthys miiuy increased during Siniperca chuatsi rhabdovirus and Vibrio anguillarum infection, suggesting that m6A may play an important role in the immune process against pathogens in fish. In addition, our study shows that stimulator of IFN genes (STING) plays a dual immune function against viruses and bacteria in fish, and through degrading STING by identifying its m6A methylation site modified by methyltransferase-like 3 (METTL3), YTH domain family 2 (YTHDF2) can weaken the IRF3 and NF-κB-driven signaling pathway, thus weakening the innate immunity and promoting the infection of Siniperca chuatsi rhabdovirus and V. anguillarum to the M. miiuy. Although there have been reports on m6A modification of STING in mammals, it is still unclear whether there is also m6A modification in lower vertebrates, especially in fish. Therefore, our study provides a reference for filling the gap of m6A modification between fish and mammals.
MeSH term(s)	Animals ; Methylation ; Antiviral Agents ; Methyltransferases/metabolism ; Gene Expression Regulation ; Signal Transduction ; Mammals/metabolism
Chemical Substances	Antiviral Agents ; Methyltransferases (EC 2.1.1.-)
Language	English
Publishing date	2023-01-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200618
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