{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:40Z","timestamp":1792786000078,"version":"4.5.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Technology Development Fund"},{"name":"Office of Technology Commercialization","id":[{"id":"https:\/\/ror.org\/02vg64e60","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Nationwide Children\u2019s Hospital","award":["AWD50001263"],"award-info":[{"award-number":["AWD50001263"]}],"id":[{"id":"https:\/\/ror.org\/003rfsp33","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000928","name":"Welch Foundation","doi-asserted-by":"publisher","award":["I-1961"],"award-info":[{"award-number":["I-1961"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA282036"],"award-info":[{"award-number":["R01CA282036"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01CA305105"],"award-info":[{"award-number":["U01CA305105"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Investigator of the Howard Hughes Medical Institute","id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sporadic inclusion body myopathy (sIBM) is the most common progressive degenerative skeletal muscle disease of older people with poorly understood pathogenesis. We assessed the involvement and impact of the noncoding RNA activated by DNA damage (NORAD) and its binding partner Pumilio (PUM) proteins on the evolution of the disease process in muscle biopsies from sIBM patients with mild or severe histopathologic changes. A disease severity\u2013dependent increase in NORAD and PUM2 expression was present along with subsarcolemmal formations of NORAD-PUM (NP) bodies in the sIBM muscles. Similarly, Norad, Pum1, and Pum2 expression levels were upregulated as disease severity increased with age in VCP-A232E mice, a model for hereditary IBM. Crossbreeding VCP-A232E mice with Norad\u2212\/\u2212 mice leading to generation of VCP mutants with either single copy or the absence of Norad showed that Norad suppresses disease progression in the VCP-A232E model in a dose-dependent manner. Norad expression in the muscle from Pum2 overexpressing mice revealed significantly increased Norad transcripts in response to high Pum2 expression and the presence of NP bodies coalescing around muscle nuclei. Collectively, these findings provide strong evidence that elevated NORAD expression is a protective, compensatory response to disease-related induction of PUM2 activity in muscle.<\/jats:p>","DOI":"10.1093\/jnen\/nlag041","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:46:58Z","timestamp":1775130418000},"page":"1164-1174","source":"Crossref","is-referenced-by-count":1,"title":["The\n                    <i>NORAD<\/i>\n                    -Pumilio regulatory axis in the evolution of inclusion body myositis"],"prefix":"10.1093","volume":"85","author":[{"given":"Lingying","family":"Tong","sequence":"first","affiliation":[{"name":"Center for Gene Therapy, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcak","family":"Ozes","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Moss","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Myers","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Hornung","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Showalter","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiy","family":"Chornyy","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua T","family":"Mendell","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, University of Texas Southwestern Medical Center , Dallas, TX,","place":["United States"]},{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center , Dallas, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2974-3943","authenticated-orcid":false,"given":"Zarife","family":"Sahenk","sequence":"additional","affiliation":[{"name":"Center for Gene Therapy, The Abigail Wexner Research Institute, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]},{"name":"Department of Pediatrics and Neurology, Nationwide Children\u2019s Hospital and The Ohio State University , Columbus, OH,","place":["United States"]},{"name":"Department of Pathology and Laboratory Medicine, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"2026092503321862900_nlag041-B1","first-page":"445","article-title":"Epidemiology of sporadic inclusion body myositis and polymyositis in Olmsted County, Minnesota","volume":"35","author":"Wilson","year":"2008","journal-title":"J Rheumatol"},{"key":"2026092503321862900_nlag041-B2","doi-asserted-by":"crossref","first-page":"e2653","DOI":"10.1212\/WNL.0000000000012004","article-title":"Epidemiology and natural history of inclusion body myositis: a 40-year population-based study","volume":"96","author":"Shelly","year":"2021","journal-title":"Neurology"},{"key":"2026092503321862900_nlag041-B3","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1093\/brain\/awr213","article-title":"Long-term observational study of sporadic inclusion body myositis","volume":"134","author":"Benveniste","year":"2011","journal-title":"Brain"},{"key":"2026092503321862900_nlag041-B4","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1001\/archneur.1991.00530240033013","article-title":"Amyloid filaments in inclusion body myositis. Novel findings provide insight into nature of filaments","volume":"48","author":"Mendell","year":"1991","journal-title":"Arch Neurol"},{"key":"2026092503321862900_nlag041-B5","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/ana.410380504","article-title":"Inclusion body myositis and myopathies","volume":"38","author":"Griggs","year":"1995","journal-title":"Ann Neurol"},{"key":"2026092503321862900_nlag041-B6","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1097\/NEN.0b013e31826183c8","article-title":"Pathogenic considerations in sporadic inclusion-body myositis, a degenerative muscle disease associated with aging and abnormalities of myoproteostasis","volume":"71","author":"Askanas","year":"2012","journal-title":"J Neuropathol Exp Neurol"},{"key":"2026092503321862900_nlag041-B7","doi-asserted-by":"crossref","first-page":"e004552","DOI":"10.1136\/bmjopen-2013-004552","article-title":"A retrospective cohort study identifying the principal pathological features useful in the diagnosis of inclusion body myositis","volume":"4","author":"Brady","year":"2014","journal-title":"BMJ Open"},{"key":"2026092503321862900_nlag041-B8","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1016\/j.jocn.2014.05.051","article-title":"Functional relevance of mitochondrial abnormalities in sporadic inclusion body myositis","volume":"21","author":"Joshi","year":"2014","journal-title":"J Clin Neurosci"},{"key":"2026092503321862900_nlag041-B9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3390\/biom9010015","article-title":"Sporadic inclusion body myositis: an acquired mitochondrial disease with extras","volume":"9","author":"De Paepe","year":"2019","journal-title":"Biomolecules"},{"key":"2026092503321862900_nlag041-B10","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.nmd.2019.02.001","article-title":"Mitochondrial DNA depletion in sporadic inclusion body myositis","volume":"29","author":"Bhatt","year":"2019","journal-title":"Neuromuscul Disord"},{"key":"2026092503321862900_nlag041-B11","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1002\/ana.410390615","article-title":"Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: a study of 56 patients","volume":"39","author":"Santorelli","year":"1996","journal-title":"Ann Neurol"},{"key":"2026092503321862900_nlag041-B12","doi-asserted-by":"crossref","first-page":"e12931","DOI":"10.1111\/bpa.12931","article-title":"Mitochondrial DNA variants in inclusion body myositis characterized by deep sequencing","volume":"31","author":"Hedberg-Oldfors","year":"2021","journal-title":"Brain Pathol"},{"key":"2026092503321862900_nlag041-B13","first-page":"889","article-title":"Light and electron microscopic immunolocalization of presenilin 1 in abnormal muscle fibers of patients with sporadic inclusion-body myositis and autosomal-recessive inclusion-body myopathy","volume":"152","author":"Askanas","year":"1998","journal-title":"Am J Pathol"},{"key":"2026092503321862900_nlag041-B14","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1080\/030097498442208","article-title":"Sporadic inclusion-body myositis and its similarities to Alzheimer disease brain. Recent approaches to diagnosis and pathogenesis, and relation to aging","volume":"27","author":"Askanas","year":"1998","journal-title":"Scand J Rheumatol"},{"key":"2026092503321862900_nlag041-B15","doi-asserted-by":"crossref","first-page":"e219-235","DOI":"10.1016\/j.lpm.2010.11.024","article-title":"Sporadic inclusion-body myositis: conformational multifactorial ageing-related degenerative muscle disease associated with proteasomal and lysosomal inhibition, endoplasmic reticulum stress, and accumulation of amyloid-beta42 oligomers and phosphorylated tau","volume":"40","author":"Askanas","year":"2011","journal-title":"Presse Med"},{"key":"2026092503321862900_nlag041-B16","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/acn3.419","article-title":"Immune and myodegenerative pathomechanisms in inclusion body myositis","volume":"4","author":"Keller","year":"2017","journal-title":"Ann Clin Transl Neurol"},{"key":"2026092503321862900_nlag041-B17","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s13311-018-0658-8","article-title":"Inclusion body myositis: update on pathogenesis and treatment","volume":"15","author":"Naddaf","year":"2018","journal-title":"Neurotherapeutics"},{"key":"2026092503321862900_nlag041-B18","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1097\/BOR.0000000000000752","article-title":"Pathogenesis of inclusion body myositis","volume":"32","author":"Greenberg","year":"2020","journal-title":"Curr Opin Rheumatol"},{"key":"2026092503321862900_nlag041-B19","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1212\/WNL.54.5.1020","article-title":"Biologically stressed muscle fibers in sporadic IBM: a clue for the enigmatic etiology?","volume":"54","author":"Karpati","year":"2000","journal-title":"Neurology"},{"key":"2026092503321862900_nlag041-B20","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1136\/jnnp.2009.174276","article-title":"Proinflammatory cell stress in sporadic inclusion body myositis muscle: overexpression of alphaB-crystallin is associated with amyloid precursor protein and accumulation of beta-amyloid","volume":"80","author":"Muth","year":"2009","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2026092503321862900_nlag041-B21","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/ana.23822","article-title":"Autoantibodies to cytosolic 5'-nucleotidase 1A in inclusion body myositis","volume":"73","author":"Pluk","year":"2013","journal-title":"Ann Neurol"},{"key":"2026092503321862900_nlag041-B22","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.bbadis.2014.09.005","article-title":"Sporadic inclusion-body myositis: a degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy","volume":"1852","author":"Askanas","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"2026092503321862900_nlag041-B23","doi-asserted-by":"crossref","first-page":"eabi9196","DOI":"10.1126\/scitranslmed.abi9196","article-title":"Loss of TDP-43 function and rimmed vacuoles persist after T cell depletion in a xenograft model of sporadic inclusion body myositis","volume":"14","author":"Britson","year":"2022","journal-title":"Sci Transl Med"},{"key":"2026092503321862900_nlag041-B24","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.ymthe.2017.02.015","article-title":"Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes","volume":"25","author":"Mendell","year":"2017","journal-title":"Mol Ther"},{"key":"2026092503321862900_nlag041-B25","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cell.2015.12.017","article-title":"Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins","volume":"164","author":"Lee","year":"2016","journal-title":"Cell"},{"key":"2026092503321862900_nlag041-B26","doi-asserted-by":"crossref","first-page":"e.42650","DOI":"10.7554\/eLife.42650","article-title":"PUMILIO hyperactivity drives premature aging of Norad-deficient mice","volume":"8","author":"Kopp","year":"2019","journal-title":"eLife"},{"key":"2026092503321862900_nlag041-B27","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41586-021-03633-w","article-title":"NORAD-induced Pumilio phase separation is required for genome stability","volume":"595","author":"Elguindy","year":"2021","journal-title":"Nature"},{"key":"2026092503321862900_nlag041-B28","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.tig.2018.09.006","article-title":"Post-transcriptional regulatory functions of mammalian Pumilio proteins","volume":"34","author":"Goldstrohm","year":"2018","journal-title":"Trends Genet"},{"key":"2026092503321862900_nlag041-B29","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ymeth.2015.11.007","article-title":"Simultaneous multicolor detection of RNA and proteins using super-resolution microscopy","volume":"98","author":"Mito","year":"2016","journal-title":"Methods"},{"key":"2026092503321862900_nlag041-B30","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1093\/hmg\/ddq050","article-title":"Transgenic mice expressing mutant forms VCP\/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone","volume":"19","author":"Custer","year":"2010","journal-title":"Hum Mol Genet"},{"key":"2026092503321862900_nlag041-B31","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00401-008-0449-0","article-title":"Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer\u2019s and Parkinson\u2019s disease brains","volume":"116","author":"Askanas","year":"2008","journal-title":"Acta Neuropathol"},{"key":"2026092503321862900_nlag041-B32","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1750-3639.2009.00290.x","article-title":"Inclusion body myositis: a degenerative muscle disease associated with intra-muscle fiber multi-protein aggregates, proteasome inhibition, endoplasmic reticulum stress and decreased lysosomal degradation","volume":"19","author":"Askanas","year":"2009","journal-title":"Brain Pathol"},{"key":"2026092503321862900_nlag041-B33","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.3390\/ijms25052742","article-title":"Sporadic inclusion body myositis at the crossroads between muscle degeneration, inflammation, and aging","volume":"25","author":"Guglielmi","year":"2024","journal-title":"Int J Molec Sci"},{"key":"2026092503321862900_nlag041-B34","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.molcel.2016.01.028","article-title":"The mitochondrial basis of aging","volume":"61","author":"Sun","year":"2016","journal-title":"Mol Cell"},{"key":"2026092503321862900_nlag041-B35","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature02517","article-title":"Premature ageing in mice expressing defective mitochondrial DNA polymerase","volume":"429","author":"Trifunovic","year":"2004","journal-title":"Nature"},{"key":"2026092503321862900_nlag041-B36","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1101\/gad.298752.117","article-title":"Post-transcriptional regulation of mouse neurogenesis by Pumilio proteins","volume":"31","author":"Zhang","year":"2017","journal-title":"Genes Dev"},{"key":"2026092503321862900_nlag041-B37","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.cell.2015.02.012","article-title":"Pumilio1 haploinsufficiency leads to SCA1-like neurodegeneration by increasing wild-type Ataxin1 levels","volume":"160","author":"Gennarino","year":"2015","journal-title":"Cell"},{"key":"2026092503321862900_nlag041-B38","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.cell.2018.02.006","article-title":"A mild PUM1 mutation is associated with adult-onset ataxia, whereas haploinsufficiency causes developmental delay and seizures","volume":"172","author":"Gennarino","year":"2018","journal-title":"Cell"},{"key":"2026092503321862900_nlag041-B39","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.molcel.2018.11.034","article-title":"The RNA-binding protein PUM2 impairs mitochondrial dynamics and mitophagy during aging","volume":"73","author":"D\u2019Amico","year":"2019","journal-title":"Molec Cell"},{"key":"2026092503321862900_nlag041-B40","doi-asserted-by":"crossref","first-page":"e25080","DOI":"10.1016\/j.heliyon.2024.e25080","article-title":"RNA binding protein PUM2 promotes IL-1beta-induced apoptosis of chondrocytes via regulating FOXO3 expression","volume":"10","author":"Wang","year":"2024","journal-title":"Heliyon"},{"key":"2026092503321862900_nlag041-B41","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1111\/jnc.13626","article-title":"Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function","volume":"138","author":"Sunitha","year":"2016","journal-title":"J Neurochem"},{"key":"2026092503321862900_nlag041-B42","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s00401-017-1731-9","article-title":"IFN-beta-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis","volume":"134","author":"Meyer","year":"2017","journal-title":"Acta Neuropathol"},{"key":"2026092503321862900_nlag041-B43","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0022-510X(88)90211-0","article-title":"Perifascicular atrophic fibers in childhood dermatomyositis with particular reference to mitochondrial changes","volume":"88","author":"Woo","year":"1988","journal-title":"J Neurol Sci"},{"key":"2026092503321862900_nlag041-B44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.neuron.2013.02.028","article-title":"Pathogenic VCP mutations induce mitochondrial uncoupling and reduced ATP levels","volume":"78","author":"Bartolome","year":"2013","journal-title":"Neuron"},{"key":"2026092503321862900_nlag041-B45","doi-asserted-by":"crossref","first-page":"e.17834","DOI":"10.7554\/eLife.17834","article-title":"Valosin-containing protein (VCP\/p97) inhibitors relieve Mitofusin-dependent mitochondrial defects due to VCP disease mutants","volume":"6","author":"Zhang","year":"2017","journal-title":"eLife"}],"container-title":["Journal of Neuropathology &amp; Experimental Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/85\/10\/1164\/68096673\/nlag041.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/85\/10\/1164\/68096673\/nlag041.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:32:28Z","timestamp":1790321548000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnen\/article\/85\/10\/1164\/8656745"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,4,17]]},"published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jnen\/nlag041","relation":{},"ISSN":["0022-3069","1554-6578"],"issn-type":[{"value":"0022-3069","type":"print"},{"value":"1554-6578","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,4,17]]}}}