{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:19:57Z","timestamp":1790353197356,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K08AR082939"],"award-info":[{"award-number":["K08AR082939"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Dermatomyositis is an autoimmune condition characterized by a high interferon signature of unknown etiology. Because coding sequences constitute &lt;1.2% of our genomes, there is a need to explore the role of the noncoding genome in disease pathogenesis. Our genomes include roughly 1.2 million Alu elements occupying approximately 10% of the genome, which can form double\u2010stranded (ds) RNA capable of triggering MDA5 leading to interferon production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We aligned muscle biopsy RNA sequencing data to the telomere\u2010to\u2010telomere reference genome and quantified short interspersed elements including Alus. Because Alus have a propensity to form dsRNA and are the major targets of both adenosine deaminase RNA specific and MDA5, we quantified adenosine to inosine (A\u2010to\u2010I) RNA editing, which reflects dsRNA in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Dermatomyositis muscle (n = 39) showed a global elevation in Alu expression (including inverted\u2010repeat Alus with high potential to form dsRNA) as well as an increased expression of unique Alu elements (n = 557,\n                      <jats:italic>q<\/jats:italic>\n                      &lt; 0.05) compared with healthy controls (n = 34), in a pattern not seen in other myositis types (n = 81). Most (75.3%) of these Alus originated from genomic regions outside genes. A cluster of the uniquely overexpressed Alus (n = 167) correlated with interferon\u2010stimulated genes and markers of myositis activity. Additionally, we found a uniquely expanded Alu A\u2010to\u2010I editome in dermatomyositis, reflecting an increase in dsRNA. Edited Alus clustered on chromosome 19, which is known to have the highest concentration of dsRNA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We hypothesize that overexpressed Alus in dermatomyositis form endogenous dsRNA that exceeds the capacity of RNA editing enzymes and triggers dsRNA sensors leading to interferon production.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.43328","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T09:14:37Z","timestamp":1753175677000},"page":"209-222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Alu Overexpression Leads to an Increased Double\u2010Stranded\n                    <scp>RNA<\/scp>\n                    Signature in Dermatomyositis"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9214-521X","authenticated-orcid":false,"given":"Rayan","family":"Najjar","sequence":"first","affiliation":[{"name":"University of Washington  Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3732-3252","authenticated-orcid":false,"given":"Andrew","family":"Mammen","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Disease, NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-8840","authenticated-orcid":false,"given":"Tomas","family":"Mustelin","sequence":"additional","affiliation":[{"name":"University of Washington  Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008128"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2018.41"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abk3112"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35057062"},{"issue":"9","key":"e_1_2_7_6_1","first-page":"1727","article-title":"Novel autoantibodies against 7SL RNA in patients with polymyositis\/dermatomyositis","volume":"32","author":"Satoh T","year":"2005","journal-title":"J Rheumatol"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-111620-100736"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2011.06.015"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1361"},{"issue":"1","key":"e_1_2_7_10_1","first-page":"59","article-title":"Whole\u2010genome expression analysis of mammalian\u2010wide interspersed repeat elements in human cell lines","volume":"24","author":"Carnevali D","year":"2017","journal-title":"DNA Res"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1801"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201900023"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00430-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05052-x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.21.6927"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.07.029"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.12.016"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01054-9"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2014.0001"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac7049"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7355"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2844-1"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11724"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1072"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx473"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1080626"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3122"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-6-31"},{"key":"e_1_2_7_33_1","article-title":"A language and environment for statistical computing. 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