A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα
ABSTRACT As the α-subunit of the high-affinity receptor for the Fc portion of immunoglobulin E (FcεRIα), FcεRIα plays a central role in IgE-mediated allergic disorders and in the immunity and immunopathology of some parasitic infections. FcεRIα is specifically expressed on basophils and mast cells,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-06-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00733-23 |
| _version_ | 1797803461302026240 |
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| author | Ruo-yu Tang Lan Yin Liang Yao Qing-Feng Zhang Xiao-Ping Chen |
| author_facet | Ruo-yu Tang Lan Yin Liang Yao Qing-Feng Zhang Xiao-Ping Chen |
| author_sort | Ruo-yu Tang |
| collection | DOAJ |
| description | ABSTRACT As the α-subunit of the high-affinity receptor for the Fc portion of immunoglobulin E (FcεRIα), FcεRIα plays a central role in IgE-mediated allergic disorders and in the immunity and immunopathology of some parasitic infections. FcεRIα is specifically expressed on basophils and mast cells, but the mechanism that controls FcεRIα expression in these cells is poorly understood. In this study, we found that the natural antisense transcript (NAT) of FcεRIα (FCER1A-AS) is co-expressed with the sense transcript (FCER1A-S) in both interleukin (IL)-3-induced FcεRIα-expressing cells and in the high FcεRIα-expressing cell line MC/9. When FCER1A-AS is selectively knocked down by the CRISPR/RfxCas13d (CasRx) approach in MC/9 cells, the expression of both FCER1A-S mRNA and proteins is markedly decreased. Furthermore, FCER1A-AS deficiency was also found to be associated with a lack of FCER1A-S expression in vivo. Correspondingly, homozygous mice deficient in FCER1A-AS demonstrated a similar phenotype to FCER1A knockout mice in Schistosoma japonicum infection and in IgE-FcεRIα-mediated cutaneous anaphylaxis. Thus, we uncovered a novel pathway for the control of FcεRIα expression by its co-expressed natural antisense transcript. IMPORTANCE FcεRIα is responsible for high-affinity binding with the Fc portion of IgE, which is critical for IgE-dependent disease responses such as allergy responses and anti-parasite immunity. FcεRIα is expressed on a few cell types, including mast cells and basophils. Although the expression of FcεRIα is known to be promoted by the IL-3-GATA-2 pathway during its differentiation, the mechanism by which FcεRIα expression is maintained remains unknown. In this study, we discovered that a natural antisense transcript, FCER1A-AS, is co-expressed with the sense transcript. The presence of FCER1A-AS is essential for sense transcript expression in mast cells and basophils, but not for the differentiation of these cells through cis-regulation. Like FcεRIα knockout mice, mice lacking FCER1A-AS also exhibit reduced survival after Schistosoma japonicum infection and a lack of IgE-mediated cutaneous anaphylaxis. Thus, a novel pathway for regulating IgE-mediated allergic diseases through noncoding RNAs has been revealed. |
| first_indexed | 2024-03-13T05:21:14Z |
| format | Article |
| id | doaj.art-5874d6e930d845eca082c2aa5a59d005 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-13T05:21:14Z |
| publishDate | 2023-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-5874d6e930d845eca082c2aa5a59d0052023-06-15T13:18:31ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.00733-23A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIαRuo-yu Tang0Lan Yin1Liang Yao2Qing-Feng Zhang3Xiao-Ping Chen4Department of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Microbiology and Immunology, School of Medicine, Tongji University, Shanghai, ChinaABSTRACT As the α-subunit of the high-affinity receptor for the Fc portion of immunoglobulin E (FcεRIα), FcεRIα plays a central role in IgE-mediated allergic disorders and in the immunity and immunopathology of some parasitic infections. FcεRIα is specifically expressed on basophils and mast cells, but the mechanism that controls FcεRIα expression in these cells is poorly understood. In this study, we found that the natural antisense transcript (NAT) of FcεRIα (FCER1A-AS) is co-expressed with the sense transcript (FCER1A-S) in both interleukin (IL)-3-induced FcεRIα-expressing cells and in the high FcεRIα-expressing cell line MC/9. When FCER1A-AS is selectively knocked down by the CRISPR/RfxCas13d (CasRx) approach in MC/9 cells, the expression of both FCER1A-S mRNA and proteins is markedly decreased. Furthermore, FCER1A-AS deficiency was also found to be associated with a lack of FCER1A-S expression in vivo. Correspondingly, homozygous mice deficient in FCER1A-AS demonstrated a similar phenotype to FCER1A knockout mice in Schistosoma japonicum infection and in IgE-FcεRIα-mediated cutaneous anaphylaxis. Thus, we uncovered a novel pathway for the control of FcεRIα expression by its co-expressed natural antisense transcript. IMPORTANCE FcεRIα is responsible for high-affinity binding with the Fc portion of IgE, which is critical for IgE-dependent disease responses such as allergy responses and anti-parasite immunity. FcεRIα is expressed on a few cell types, including mast cells and basophils. Although the expression of FcεRIα is known to be promoted by the IL-3-GATA-2 pathway during its differentiation, the mechanism by which FcεRIα expression is maintained remains unknown. In this study, we discovered that a natural antisense transcript, FCER1A-AS, is co-expressed with the sense transcript. The presence of FCER1A-AS is essential for sense transcript expression in mast cells and basophils, but not for the differentiation of these cells through cis-regulation. Like FcεRIα knockout mice, mice lacking FCER1A-AS also exhibit reduced survival after Schistosoma japonicum infection and a lack of IgE-mediated cutaneous anaphylaxis. Thus, a novel pathway for regulating IgE-mediated allergic diseases through noncoding RNAs has been revealed.https://journals.asm.org/doi/10.1128/spectrum.00733-23antisense RNAFcεRIαFCER1A-ASIgEallergic reactionSchistosoma japonicum |
| spellingShingle | Ruo-yu Tang Lan Yin Liang Yao Qing-Feng Zhang Xiao-Ping Chen A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα Microbiology Spectrum antisense RNA FcεRIα FCER1A-AS IgE allergic reaction Schistosoma japonicum |
| title | A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα |
| title_full | A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα |
| title_fullStr | A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα |
| title_full_unstemmed | A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα |
| title_short | A Co-Expressed Natural Antisense RNA FCER1A-AS Controls IgE-Dependent Immunity by Promoting Expression of FcεRIα |
| title_sort | co expressed natural antisense rna fcer1a as controls ige dependent immunity by promoting expression of fcεriα |
| topic | antisense RNA FcεRIα FCER1A-AS IgE allergic reaction Schistosoma japonicum |
| url | https://journals.asm.org/doi/10.1128/spectrum.00733-23 |
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