The long noncoding RNA NARL regulates immune responses via microRNA-mediated NOD1 downregulation in teleost fish

Abstract

Increasing evidence shows that the long noncoding RNA (lncRNA) is a major regulator and participates in the regulation of various physiological and pathological processes, such as cell proliferation, differentiation, metastasis, and apoptosis. Unlike mammals, however, the study of lncRNA in lower invertebrates is just beginning and the extent of lncRNA-mediate regulation remains unclear. Here, we for the first time identify an lncRNA, termed nucleotide oligomerization domain 1 (NOD1) antibacterial and antiviral-related lncRNA (NARL), as a key regulator for innate immunity in teleost fish. We found that NOD1 plays an important role in the antibacterial and antiviral process in fish and that the microRNA miR-217-5p inhibits NOD1 expression and thus weakens the NF-κB and the IRF3-driven signaling pathway. Furthermore, our results indicated that NARL functions as a competing endogenous RNA (ceRNA) for miR-217-5p to regulate protein abundance of NOD1; thus, invading microorganisms are eliminated and immune responses are promoted. Our study also demonstrates the regulation mechanism that lncRNA NARL can competitive adsorption miR-217-5p to regulate the miR-217-5p/NOD1 axis is widespread in teleost fish. Taken together, our results reveal that NARL in fish is a critical positive regulator of innate immune responses to viral and bacterial infection by suppressing a feedback to NOD1-NF-κB/IRF3-mediated signaling. Increasing evidence shows that the long noncoding RNA (lncRNA) is a major regulator and participates in the regulation of various physiological and pathological processes, such as cell proliferation, differentiation, metastasis, and apoptosis. Unlike mammals, however, the study of lncRNA in lower invertebrates is just beginning and the extent of lncRNA-mediate regulation remains unclear. Here, we for the first time identify an lncRNA, termed nucleotide oligomerization domain 1 (NOD1) antibacterial and antiviral-related lncRNA (NARL), as a key regulator for innate immunity in teleost fish. We found that NOD1 plays an important role in the antibacterial and antiviral process in fish and that the microRNA miR-217-5p inhibits NOD1 expression and thus weakens the NF-κB and the IRF3-driven signaling pathway. Furthermore, our results indicated that NARL functions as a competing endogenous RNA (ceRNA) for miR-217-5p to regulate protein abundance of NOD1; thus, invading microorganisms are eliminated and immune responses are promoted. Our study also demonstrates the regulation mechanism that lncRNA NARL can competitive adsorption miR-217-5p to regulate the miR-217-5p/NOD1 axis is widespread in teleost fish. Taken together, our results reveal that NARL in fish is a critical positive regulator of innate immune responses to viral and bacterial infection by suppressing a feedback to NOD1-NF-κB/IRF3-mediated signaling. Innate immunity is the first line of host defense and mainly composes of pattern recognition receptors (PRRs) and their signal pathways. Nucleotide-binding oligomerization domain-like receptors (NLRs) are part of the cytosolic PRRs and play key roles in response to various bacterial infections (1Girardin S.E. Jéhanno M. Mengin-Lecreulx D. Sansonetti P.J. Alzari P.M. Philpott D.J. Identification of the critical residues involved in peptidoglycan detection by Nod1.J. Biol. Chem. 2005; 280: 38648-38656Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar). As the members of the NLR family, nucleotide oligomerization domain (NOD) 1 and NOD2 are important for epithelial and myeloid cell signaling in response to cytosolic bacterial peptidoglycans, muramyl dipeptide (MDP) and G-D-glutamyl-mesodiaminopimelic acid (iE-DAP) (2Caruso R. Warner N. Inohara N. Núñez G. NOD1 and NOD2: Signaling, host defense, and inflammatory disease.Immunity. 2014; 41: 898-908Abstract Full Text Full Text PDF PubMed Scopus (342) Google Scholar, 3Philpott D.J. Sorbara M.T. Robertson S.J. Croitoru K. Girardin S.E. NOD proteins: Regulators of inflammation in health and disease.Nat. Rev. Immunol. 2014; 14: 9-23Crossref PubMed Scopus (368) Google Scholar). NOD1 can monitor bacterial intrusions in cells and promotes the activation of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways through RIP2 kinase (4Fritz T. Niederreiter L. Adolph T. Blumberg R.S. Kaser A. Crohn's disease: NOD2, autophagy and ER stress converge.Gut. 2011; 60: 1580-1588Crossref PubMed Scopus (146) Google Scholar, 5Park J.-H. Kim Y.-G. McDonald C. Kanneganti T.-D. Hasegawa M. Body-Malapel M. Inohara N. Nunez G. RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs.J. Immunol. 2007; 178: 2380-2386Crossref PubMed Scopus (361) Google Scholar). In lower vertebrates, increasing pieces of evidence show that NOD1 is widespread in fish and participates in the regulation of antibacterial immune response after pathogen infection (6Li J. Gao Y. Xu T. Comparative genomic and evolution of vertebrate NOD1 and NOD2 genes and their immune response in miiuy croaker.Fish. Shellfish Immunol. 2015; 46: 387-397Crossref PubMed Scopus (27) Google Scholar, 7Park S.B. Hikima J.-I. Suzuki Y. Ohtani M. Nho S.W. Cha I.S. Jang H.B. Kondo H. Hirono I. Aoki T. Molecular cloning and functional analysis of nucleotide-binding oligomerization domain 1 (NOD1) in olive flounder, Paralichthys olivaceus.Dev. Comp. Immunol. 2012; 36: 680-687Crossref PubMed Scopus (39) Google Scholar, 8Swain B. Basu M. Samanta M. NOD1 and NOD2 receptors in mrigal (Cirrhinus mrigala): Inductive expression and downstream signalling in ligand stimulation and bacterial infections.J. Biosci. 2013; 38: 533-548Crossref PubMed Scopus (33) Google Scholar, 9Bi D. Gao Y. Chu Q. Cui J. Xu T. NOD1 is the innate immune receptor for iE-DAP and can activate NF-κB pathway in teleost fish.Dev. Comp. Immunol. 2017; 76: 238-246Crossref PubMed Scopus (25) Google Scholar, 10Bi D. Wang Y. Gao Y. Li X. Chu Q. Cui J. Xu T. Recognition of lipopolysaccharide and activation of NF-κB by cytosolic sensor NOD1 in teleost fish.Front. Immunol. 2018; 9: 1413Crossref PubMed Scopus (28) Google Scholar). Recently, researchers have demonstrated that fish NOD1 plays an important role in recognizing lipopolysaccharides (LPS) and iE-DAP, as well as initiating downstream antiviral signaling pathways by identifying RNA virus (9Bi D. Gao Y. Chu Q. Cui J. Xu T. NOD1 is the innate immune receptor for iE-DAP and can activate NF-κB pathway in teleost fish.Dev. Comp. Immunol. 2017; 76: 238-246Crossref PubMed Scopus (25) Google Scholar, 10Bi D. Wang Y. Gao Y. Li X. Chu Q. Cui J. Xu T. Recognition of lipopolysaccharide and activation of NF-κB by cytosolic sensor NOD1 in teleost fish.Front. Immunol. 2018; 9: 1413Crossref PubMed Scopus (28) Google Scholar, 11Wu X.M. Zhang J. Li P.W. Hu Y.W. Cao L. Ouyang S. Bi Y.H. Nie P. Chang M.X. NOD1 promotes antiviral signaling by binding viral RNA and regulating the interaction of MDA5 and MAVS.J. Immunol. 2020; 204: 2216-2231Crossref PubMed Scopus (13) Google Scholar). Unlike mammals, TLR4, as the central protein that recognizes LPS, does not exist in most fish. Therefore, it was found that fish NOD1 can recognize LPS and iE-DAP and eventually causes an inflammatory response that could elucidate the resistance of fish against bacterial infections. Recently, a series of regulatory factors involved in the regulation of the NOD1 signaling pathway has been found. CENTB1 and E3 Ligase RNF34 regulate the NOD1 signaling pathway through directly regulating the expression of NOD1 (12Yamamoto-Furusho J.K. Barnich N. Xavier R. Hisamatsu T. Podolsky D.K. Centaurin β1 down-regulates nucleotide-binding oligomerization domains 1-and 2-dependent NF-κB activation.J. Biol. Chem. 2006; 281: 36060-36070Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar, 13Zhang R. Zhao J. Song Y. Wang X. Wang L. Xu J. Song C. Liu F. The E3 ligase RNF34 is a novel negative regulator of the NOD1 pathway.Cell. Physiol. Biochem. 2014; 33: 1954-1962Crossref PubMed Scopus (13) Google the the NOD1 signal pathway by regulating the of NOD1 of Nod1 by 2005; PubMed Scopus Google it was also found that can as a positive regulator of the NOD1 signaling pathway J. Y. N. R. is for Nod1 S. A. 2007; PubMed Scopus Google Scholar). In to protein regulatory microRNA has also been found to play an important role in the NOD1 signaling pathway in could NOD1 and regulate H. Y. A. H. Kim J. Chang regulation of NOD1 by 2017; PubMed Scopus Google Scholar). NOD1 is an important receptor that recognizes LPS in the of the regulatory mechanism of the NOD1 signaling pathway in fish is Our found for the first time that and miR-217-5p can and regulate the expression of NOD1 to the inflammatory response in fish Q. Bi D. Xu T. immune responses by NOD1 in the teleost fish 2020; Scopus Google Scholar). The long noncoding RNA (lncRNA) is as RNA noncoding and G. A. M. S. S. K. S. T. of of the PubMed Scopus Google Scholar, S. A. A. T. A. A. J. F. of in 2012; PubMed Scopus Google Scholar). increasing of have that lncRNA is a major regulator and participates in the regulation of cell proliferation, differentiation, metastasis, and M. in disease.Nat. Rev. 2011; PubMed Scopus Google Scholar, Rev. PubMed Scopus Google Scholar). also show that can play the role of competitive endogenous (ceRNA) by thus regulating the binding of and the of has been in and such as lncRNA can as to to regulate J. Zhang H. Cui as inhibits by to regulate expression and the 2018; PubMed Scopus Google Scholar, X. Y. S. Wang P. through Rev. Google Scholar, X. H. X. Li B. functions in cell by PubMed Scopus Google Scholar). the mechanism of lncRNA in lower is is a of lower and an important part of vertebrate it is an in The teleost fish not has a important in evolution and immunity but also in the is not to are to various and RNA such as and M. R. and for fish 2020; PubMed Scopus Google Scholar, M. M. Y. J. S. L. Y. A. K. S. role for NOD1 in host recognition of bacterial peptidoglycan Immunol. PubMed Scopus Google Scholar). The mechanism that fish and to and fish are that to and LPS and iE-DAP are by various and can an inflammatory response in the host M. S. in response to bacterial receptor and receptor 2014; PubMed Scopus Google Scholar, Q. Y. Cui J. Xu T. the NF-κB pathway in teleost fish by Immunol. 2017; PubMed Scopus Google Scholar). the mechanism of and RNA virus has been in the process of teleost fish is that of and has and as the of and in In we a regulatory involved in innate immune responses in teleost fish. Our has that miR-217-5p can regulate NOD1 and the antibacterial immune response in miiuy Q. Bi D. Xu T. immune responses by NOD1 in the teleost fish 2020; Scopus Google Scholar). we that miR-217-5p can regulate NOD1 and can the antiviral response in miiuy Furthermore, we found that an lncRNA, can as a for miR-217-5p to NOD1 thus innate immune Our not to the of the mechanism in teleost fish but also a for the of lncRNA in the innate immune response in lower Increasing pieces of have that lncRNA can play a regulatory role as a and the immune signaling pathways through the mechanism T. K. L. Zhang J. X. X. B. Wang A. Liu J. and to activate NF-κB pathway and proliferation, and resistance of 2020; Scopus Google Scholar). We miiuy LPS and to identify are involved in the regulation of and the expression of in the of the and the was by In lncRNA found. The of of was and the of most was As in we found that a lncRNA NARL to the is in the genes after LPS stimulation and infection the of the was and demonstrated that the of NARL was and miiuy N. and L. and and of we that NARL was mainly in the by in cells and in cells NARL an protein is in and the that NARL has a We first the NARL expression LPS stimulation to the results of As in we found that the expression of NARL was after LPS and against NARL and and the of NARL to the functions of As can the expression of and could we to the the NARL could NARL expression and genes play an important role in the innate immune thus, we the of NARL in regulating the expression of inflammatory and As in NARL can the expression of and LPS NARL also can the expression of and infection Furthermore, cell analysis that NARL the of cells We and to cell and cell for the role of NARL in innate As in and the results that of NARL the of cells and cell it NARL was have indicated that the of LPS can cell S. Y. the of cells LPS by 2020; PubMed Scopus Google Scholar). results that NARL can the and of miiuy cell the that NARL plays as a positive in regulating inflammatory as well as cell and cell The in cell and cell are a of the regulation of NARL innate immune In NARL can regulate the antibacterial responses antiviral response and the expression of inflammatory antiviral the of pathogen to cell proliferation, and cell apoptosis. have been to as by binding T. K. L. Zhang J. X. X. B. Wang A. Liu J. and to activate NF-κB pathway and proliferation, and resistance of 2020; Scopus Google Scholar, C. Gao Q. Wang M. H. to the regulation of myeloid cell by Physiol. 2020; PubMed Scopus Google Scholar). the we have been to that NARL is mainly in the Therefore, to NARL as a we first the the and the expression We the in As in NARL is in that the can directly to we and to that can NARL and that the and to have a of to we to in cells NARL expression and the shows that the expression of miR-217-5p is the we found that the expression of miR-217-5p the NARL was NARL can miR-217-5p we miR-217-5p The miR-217-5p sensor was by of miR-217-5p the we the miR-217-5p sensor NARL that NARL it Taken together, that NARL could regulate miR-217-5p expression and and NARL as a of We the of NARL and found a binding for miR-217-5p to NARL can directly we the NARL and the the miR-217-5p binding The shows that miR-217-5p and can the NARL but have the In we the the of NARL the and miR-217-5p to that miR-217-5p can the of As in miR-217-5p can the of but the of the of the the has been to the expression of protein results that NARL miR-217-5p through the miR-217-5p the we have that NARL could directly to We thus the of NARL to to the are in cells by and The results analysis that NARL and miR-217-5p by the interaction NARL and we to NARL can by cells that NARL a for The that miR-217-5p could by NARL we that recognize by We the the and the of NARL we a expression of and to protein and the protein can to and also Therefore, can to miR-217-5p can by the of results that the miR-217-5p of NARL was that of NARL and In results indicated that NARL can directly to and NARL as a of the role of miR-217-5p against the innate immune miR-217-5p and miR-217-5p cells and by LPS, The results that inflammatory and are by the of miR-217-5p miR-217-5p LPS Furthermore, we found that miR-217-5p miR-217-5p also could genes and Here, we that the of the miR-217-5p the expression of of the innate immune response genes is not but are we that to the of and of miR-217-5p is not in and genes cells for that NOD1 can by The results that miR-217-5p could the and by NOD1 Furthermore, we the of miR-217-5p and cell proliferation, the results that miR-217-5p cell and cell LPS stimulation and our we can that an immune response of to cell and of cell immune response of and genes cell and cell miR-217-5p the expression of by the expression of thus cell and cell In miR-217-5p plays an important regulatory role in inflammatory immune that NARL miR-217-5p and miR-217-5p and we NARL is to regulate NOD1 protein expression is NARL is in cells of the NOD1 protein expression was through NARL of NARL expression is cells and NOD1 expression by The results show that NARL can NOD1 expression NARL NOD1 expression results indicated that miR-217-5p can NOD1 NARL can the of miR-217-5p NOD1 the cells miR-217-5p and and the that NARL could the of miR-217-5p NOD1 protein expression the NOD1 NARL and various The results that NARL could the negative of miR-217-5p the of and genes we to the of the regulatory cell The results indicated that of NARL could the negative of miR-217-5p cell LPS stimulation We and cells to the results that NARL NOD1 by the results show that can the negative of the NOD1 demonstrated that NARL as a for miR-217-5p to regulate NOD1 the of our we first the of vertebrate as in miR-217-5p to fish. the miR-217-5p binding in NOD1 also to fish the evidence that miR-217-5p could NOD1 fish by cloning of L. and N. the of miR-217-5p binding as a miR-217-5p to the of L. and N. it shows the of cells their results that miR-217-5p can the NOD1 in fish that miR-217-5p is and is also to we also the that miR-217-5p regulating lncRNA NARL also in we the of NARL the of NARL is fish NARL in in the binding of miR-217-5p we of L. and N. NARL and their miR-217-5p binding to NARL in fish could also that miR-217-5p can the of the of NARL in but it has Furthermore, to L. and N. NARL can miR-217-5p we and found that L. and N. NARL could the of miR-217-5p NOD1 results that NARL as endogenous RNA to miR-217-5p fish. of that NARL fish is important for their the host defense against pathogen and the of the immune to an immune the host recognizes the of it a series of signal that the activation of NF-κB and to the of inflammatory and antiviral factors such as and innate immune The of infections and immune and inflammatory of inflammatory can to inflammatory Therefore, of and mechanism are to the of the immune In host genes not and are a we an interaction regulating teleost antibacterial and antiviral signaling pathways. miR-217-5p can the expression of NOD1 and innate immune for bacterial viral infection G. A. M. S. S. K. S. T. of of the PubMed Scopus Google Scholar). Furthermore, in the our results show that NARL as an endogenous RNA to miR-217-5p and the inflammatory responses and antiviral In NARL can an increasing of miR-217-5p LPS thus the of antibacterial and antiviral immune and immune The the critical roles of long noncoding in innate immune responses by bacterial RNA viral infection and that regulation mechanism in teleost fish. play a role in recognizing bacterial viral and as of the most members of is in of A. I. in cell and Rev. 2014; PubMed Scopus Google Scholar). As an NOD1 can the by various in (2Caruso R. Warner N. Inohara N. Núñez G. NOD1 and NOD2: Signaling, host defense, and inflammatory disease.Immunity. 2014; 41: 898-908Abstract Full Text Full Text PDF PubMed Scopus (342) Google Scholar). Recently, increasing have that NOD1 in teleost fish can activate the NF-κB signaling pathway and the host to various inflammatory to bacterial (9Bi D. Gao Y. Chu Q. Cui J. Xu T. NOD1 is the innate immune receptor for iE-DAP and can activate NF-κB pathway in teleost fish.Dev. Comp. Immunol. 2017; 76: 238-246Crossref PubMed Scopus (25) Google Scholar, 10Bi D. Wang Y. Gao Y. Li X. Chu Q. Cui J. Xu T. Recognition of lipopolysaccharide and activation of NF-κB by cytosolic sensor NOD1 in teleost fish.Front. Immunol. 2018; 9: 1413Crossref PubMed Scopus (28) Google Scholar). In NOD1 in fish can also as the receptor of the RNA virus to the immune response in the virus infection X.M. Zhang J. Li P.W. Hu Y.W. Cao L. Ouyang S. Bi Y.H. Nie P. Chang M.X. NOD1 promotes antiviral signaling by binding viral RNA and regulating the interaction of MDA5 and MAVS.J. Immunol. 2020; 204: 2216-2231Crossref PubMed Scopus (13) Google Scholar). In a series of regulatory factors have been to in the regulation of signal pathways in mammals, genes (12Yamamoto-Furusho J.K. Barnich N. Xavier R. Hisamatsu T. Podolsky D.K. Centaurin β1 down-regulates nucleotide-binding oligomerization domains 1-and 2-dependent NF-κB activation.J. Biol. Chem. 2006; 281: 36060-36070Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar, 13Zhang R. Zhao J. Song Y. Wang X. Wang L. Xu J. Song C. Liu F. The E3 ligase RNF34 is a novel negative regulator of the NOD1 pathway.Cell. Physiol. Biochem. 2014; 33: 1954-1962Crossref PubMed Scopus (13) Google Scholar, of Nod1 by 2005; PubMed Scopus Google Scholar, J. Y. N. R. is for Nod1 S. A. 2007; PubMed Scopus Google and noncoding genes H. Y. A. H. Kim J. Chang regulation of NOD1 by 2017; PubMed Scopus Google Scholar). Unlike mammals, the of NOD1 and signal pathway in teleost fish has just Therefore, the the regulation of fish NOD1 signaling pathway is we for the first time that and miR-217-5p can the expression of NOD1 the the inflammatory response by NOD1 and the immune in fish Q. Bi D. Xu T. immune responses by NOD1 in the teleost fish 2020; Scopus Google Scholar). In the we found that the miR-217-5p/NOD1 axis can by to a immune Here, we that NARL as a to in innate immune responses in fish. The of a of noncoding is that of are noncoding P.J. A. T. pathways and of NOD1 and Rev. Immunol. 2006; PubMed Scopus Google Scholar). We to that not as lncRNA, and have been in Unlike most genes that can genes by the of the Increasing evidence that are not genomic but a of that have regulatory the genes in is that lncRNA such as the lncRNA has C. N. of the genomic in of and but evolution of PubMed Scopus Google Scholar). it is that lncRNA also can functions negative and the evolution of 2014; PubMed Scopus Google Scholar). In the we the of NARL and found that it is fish miiuy and analysis can a to study functional Therefore, the of lncRNA NARL of functions in has also been by the of lncRNA is such as the binding evolution of noncoding of does not of 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). Here, we show an lncRNA NARL can NOD1 expression through miR-217-5p in miiuy the miR-217-5p NARL have been teleost that NARL a in fish Our study that fish NOD1 plays an role in the innate antibacterial response (9Bi D. Gao Y. Chu Q. Cui J. Xu T. NOD1 is the innate immune receptor for iE-DAP and can activate NF-κB pathway in teleost fish.Dev. Comp. Immunol. 2017; 76: 238-246Crossref PubMed Scopus (25) Google Scholar, 10Bi D. Wang Y. Gao Y. Li X. Chu Q. Cui J. Xu T. Recognition of lipopolysaccharide and activation of NF-κB by cytosolic sensor NOD1 in teleost fish.Front. Immunol. 2018; 9: 1413Crossref PubMed Scopus (28) Google the researchers fish NOD1 that promotes antiviral signaling by binding viral RNA and regulating the interaction of MDA5 and X.M. Zhang J. Li P.W. Hu Y.W. Cao L. Ouyang S. Bi Y.H. Nie P. Chang M.X. NOD1 promotes antiviral signaling by binding viral RNA and regulating the interaction of MDA5 and MAVS.J. Immunol. 2020; 204: 2216-2231Crossref PubMed Scopus (13) Google Scholar). In we that miR-217-5p plays a negative NARL a positive regulatory role in regulating inflammatory responses and antiviral Furthermore, we that NARL as a regulator of inflammatory responses and antiviral responses as a for miR-217-5p to NOD1 thus, immune and immune are Our the critical roles of in fish innate immune response processes, for the vertebrate and the evolution of immune was was in for The was as Q. Y. Cui J. Xu T. the NF-κB pathway in teleost fish by Immunol. 2017; PubMed Scopus Google Scholar, L. Chu Q. Chang R. Xu T. inhibits IRF3-driven immune responses in lower through Immunol. 2020; PubMed Scopus Google Scholar). fish was of LPS through As of physiological was to the time and the for RNA in the of for the and of and the by the of The and LPS fish and the for the of the The The RNA the miiuy Xu Wang Wang Li Wang Liu Liu J. Wang A. J. Chu Q. Q. The of the miiuy innate immune and PubMed Scopus Google to by noncoding to the in to noncoding that been as noncoding RNA S.W. A. J. J. to the RNA 2015; PubMed Scopus Google Scholar). as M. miiuy cells M. miiuy cells and M. miiuy cells in and cells in and in stimulation cells LPS of and for RNA NOD1 expression of M. NOD1 of M. and as Q. Bi D. Xu T. immune responses by NOD1 in the teleost fish 2020; Scopus Google Scholar). NARL the of NARL in M. N. and L. The in the miR-217-5p binding the of NARL the the of NARL expression by cloning the NARL of M. N. and L. the was the and of and the NARL was and The in the miR-217-5p binding miR-217-5p sensor was by miR-217-5p the The of the was by and through the and to the The miR-217-5p are The miR-217-5p and The negative RNA and are that and their in the RNA pathway. The miR-217-5p was The negative was The RNA for NARL is as was was The negative RNA was and nuclear RNA and RNA cells the RNA to the RNA was and was by RNA of RNA to genomic The nuclear and cytosolic the RNA to the expression was by The RNA was by and was to of The expression analysis of miR-217-5p was by the was in an and as negative to lncRNA, and are in The NARL and the of the miR-217-5p binding miR-217-5p the the functional regulation of NARL cells NOD1 expression NARL expression and Q. Bi D. Xu T. immune responses by NOD1 in the teleost fish 2020; Scopus Google miR-217-5p negative the cells for the The miR-217-5p sensor was miR-217-5p NARL expression the cells for the against the The of was in in of to for and and in The protein in the cell was the protein detection to and to by The is was The against NOD1 was and The results of The by The was a NARL and miR-217-5p binding in The the RNA and RNA and an The cells for 1 The by RNA was the and was to the expression of The of as Q. Xu T. Chang R. Zhang L. noncoding RNA antiviral responses through in lower 2020; PubMed Scopus Google Scholar, T. Chu Q. Cui J. antiviral innate immune response in Immunol. 2018; PubMed Scopus Google Scholar). NARL is involved in the regulation cells miR-217-5p for RNA that NARL has the to directly to cells for In cells after and and the RNA was the and the expression of was by Q. Xu T. Chang R. Zhang L. noncoding RNA antiviral responses through in lower 2020; PubMed Scopus Google Scholar). was after in to the D. Wang Y. Gao Y. Li X. Chu Q. Cui J. Xu T. Recognition of lipopolysaccharide and activation of NF-κB by cytosolic sensor NOD1 in teleost fish.Front. Immunol. 2018; 9: 1413Crossref PubMed Scopus (28) Google Scholar). the cell was cell the the in The was an and The of and cells was to the Liu Y. X. virus the of to of Immunol. 2018; PubMed Scopus Google Scholar). are as the was to the The expression was the and by analysis of by of expression and the PubMed Scopus Google Scholar). of was RNA have been in the the for and are the The that have of the of study was by of and and T. and the Q. T. the Q. T. the Q. Q. T. the

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