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SLE autoantibodies often target nucleic acids, including RNAs and specifically RNA domains with higher-order structural content. We report that autoantibodies directed against neuronal regulatory brain cytoplasmic (BC) RNAs were generated in a subset of SLE patients. By contrast, anti-BC RNA autoantibodies (anti-BC abs) were not detected in sera from patients with autoimmune diseases other than SLE (e.g., rheumatoid arthritis or multiple sclerosis) or in sera from healthy subjects with no evidence of disease. SLE anti-BC abs belong to the IgG class of immunoglobulins and target both primate BC200 RNA and rodent BC1 RNA. They are specifically directed at architectural motifs in BC RNA 5\u2032 stem\u2013loop domains that serve as dendritic targeting elements (DTEs). SLE anti-BC abs effectively compete with RNA transport factor heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2) for DTE access and significantly diminish BC RNA delivery to synapto-dendritic sites of function.<jats:italic>In vivo<\/jats:italic>experiments with male BALB\/c mice indicate that, upon lipopolysaccharide-induced opening of the blood\u2013brain barrier, SLE anti-BC abs are taken up by CNS neurons where they significantly impede localization of endogenous BC1 RNA to synapto-dendritic domains. Lack of BC1 RNA causes phenotypic abnormalities including epileptogenic responses and cognitive dysfunction. The combined data indicate a role for anti-BC RNA autoimmunity in SLE and its neuropsychiatric manifestations.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>Although clinical manifestations of neuropsychiatric lupus are well recognized, the underlying molecular\u2013cellular alterations have been difficult to determine. We report that sera of a subset of lupus patients contain autoantibodies directed at regulatory brain cytoplasmic (BC) RNAs. These antibodies, which we call anti-BC abs, target the BC RNA 5\u2032 domain noncanonical motif structures that specify dendritic delivery. Lupus anti-BC abs effectively compete with RNA transport factor heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2) for access to BC RNAs. As a result, hnRNP A2 is displaced, and BC RNAs are impaired in their ability to reach synapto-dendritic sites of function. The results reveal an unexpected link between BC RNA autoantibody recognition and dendritic RNA targeting. Cellular RNA dysregulation may thus be a contributing factor in the pathogenesis of neuropsychiatric lupus.<\/jats:p>","DOI":"10.1523\/jneurosci.1657-18.2019","type":"journal-article","created":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T21:45:13Z","timestamp":1565646313000},"page":"7759-7777","source":"Crossref","is-referenced-by-count":17,"title":["Neuronal BC RNA Transport Impairments Caused by Systemic Lupus Erythematosus Autoantibodies"],"prefix":"10.1523","volume":"39","author":[{"given":"Ilham A.","family":"Muslimov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Iacoangeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taesun","family":"Eom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madisen","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Stephenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M.","family":"Ginzler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6995-3833","authenticated-orcid":false,"given":"Henri","family":"Tiedge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2019,8,12]]},"reference":[{"key":"2023041803375134000_39.39.7759.1","doi-asserted-by":"publisher","DOI":"10.1191\/0961203303lu501oa"},{"key":"2023041803375134000_39.39.7759.2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199904)42:4<599::AID-ANR2>3.0.CO;2-F"},{"key":"2023041803375134000_39.39.7759.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021933"},{"key":"2023041803375134000_39.39.7759.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-052814-023338"},{"key":"2023041803375134000_39.39.7759.5","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.16.1693"},{"key":"2023041803375134000_39.39.7759.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00311-2"},{"key":"2023041803375134000_39.39.7759.7","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.3.507"},{"key":"2023041803375134000_39.39.7759.8","doi-asserted-by":"publisher","DOI":"10.1101\/lm.045617.117"},{"key":"2023041803375134000_39.39.7759.9","doi-asserted-by":"publisher","DOI":"10.1177\/0961203308094362"},{"key":"2023041803375134000_39.39.7759.10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.491001"},{"key":"2023041803375134000_39.39.7759.11","doi-asserted-by":"publisher","DOI":"10.3109\/08916930903374865"},{"key":"2023041803375134000_39.39.7759.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.9.2624"},{"key":"2023041803375134000_39.39.7759.13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4172\/2155-9899.1000134","article-title":"Antibodies to an intracellular antigen penetrate neuronal cells and cause deleterious effects","volume":"4","author":"Douglas","year":"2013","journal-title":"J Clin Cell Immunol"},{"key":"2023041803375134000_39.39.7759.14","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0895"},{"key":"2023041803375134000_39.39.7759.15","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0889-857X(21)00733-X","article-title":"Antiribosomal antibodies in systemic lupus erythematosus","volume":"18","author":"Elkon","year":"1992","journal-title":"Rheum Dis Clin North Am"},{"key":"2023041803375134000_39.39.7759.16","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.05885-11"},{"key":"2023041803375134000_39.39.7759.17","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201401005"},{"key":"2023041803375134000_39.39.7759.18","doi-asserted-by":"crossref","unstructured":"Eom T , Muslimov IA , Iacoangeli A , Tiedge H (2018) Dendritic targeting and regulatory RNA control of local neuronal translation. 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