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Adv."],"published-print":{"date-parts":[[2026,6,19]]},"abstract":"<jats:p>\n                    Age-related decline in oocyte quality increases the risk of infertility, miscarriage, and birth defects. Mitochondrial dysfunction is a key contributor to this decline. Here, we report that oocyte-specific deletion of\n                    <jats:italic toggle=\"yes\">Uba3<\/jats:italic>\n                    , which encodes the catalytic subunit of the E1 NEDDylation-activating complex, causes sterility in mice. Fully grown, germinal vesicle\u2013stage\n                    <jats:italic toggle=\"yes\">Uba3<\/jats:italic>\n                    conditional knockout oocytes exhibit mitochondrial dysfunction, including elevated reactive oxygen species, impaired oxidative phosphorylation, and depletion of mitochondrially encoded RNA transcripts. Proteomic analysis identified alterations in mitochondrial-associated proteins, including enrichment of mitochondrial matrix and respiratory chain components and reduced abundance of electron transport chain complexes. These defects were associated with reduced levels of the mitochondrial RNA polymerase, POLRMT [polymerase (RNA) mitochondrial DNA directed]. We further show that POLRMT is directly modified by NEDDylation, which alters its stability by antagonizing ubiquitylation and degradation. Notably, NEDD8 levels decline with age in both mouse and human oocytes. Together, these findings identify NEDDylation as a regulator of oocyte quality and connect this pathway to mitochondrial transcription in oocytes.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec3505","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T18:00:26Z","timestamp":1781719226000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["NEDDylation maintains oocyte quality by stabilizing mitochondrial transcription"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6040-7166","authenticated-orcid":true,"given":"Avery A.","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA."},{"name":"Graduate Program in Development, Disease Models, and Therapeutics, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3949-930X","authenticated-orcid":true,"given":"Tessa E.","family":"Steenwinkel","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA."},{"name":"Graduate Program in Development, Disease Models, and Therapeutics, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1739-0338","authenticated-orcid":true,"given":"Bethany K.","family":"Patton","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8033-1639","authenticated-orcid":true,"given":"Peixin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0680-6123","authenticated-orcid":true,"given":"Matthew D.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Shared Equipment Authority, Rice University, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3021-0875","authenticated-orcid":true,"given":"Jaspreet K.","family":"Rishi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7231-8665","authenticated-orcid":true,"given":"Mei","family":"Leng","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4166-9555","authenticated-orcid":true,"given":"Alexander B.","family":"Saltzman","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-921X","authenticated-orcid":true,"given":"Elizabeth S.","family":"Anaya","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, USA."},{"name":"Graduate Program in Cancer and Cellular Biology, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8876-9946","authenticated-orcid":true,"given":"Momal","family":"Sharif","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie J.","family":"McKenzie","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA."},{"name":"Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6868-7185","authenticated-orcid":true,"given":"Laura","family":"Detti","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, 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