{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:47:51Z","timestamp":1784090871376,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["IB83 3-4"],"award-info":[{"award-number":["IB83 3-4"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["GRK1789"],"award-info":[{"award-number":["GRK1789"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["CRC1506"],"award-info":[{"award-number":["CRC1506"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mutations in a broad variety of genes can provoke the severe childhood disorder trichothiodystrophy (TTD) that is classified as a DNA repair disease or a transcription syndrome of RNA polymerase II. In an attempt to identify the common underlying pathomechanism of TTD we performed a knockout\/knockdown of the two unrelated TTD factors TTDN1 and RNF113A and investigated the consequences on ribosomal biogenesis and performance. Interestingly, interference with these TTD factors created a nearly uniform impact on RNA polymerase I transcription with downregulation of UBF, disturbed rRNA processing and reduction of the backbone of the small ribosomal subunit rRNA 18S. This was accompanied by a reduced quality of decoding in protein translation and the accumulation of misfolded and carbonylated proteins, indicating a loss of protein homeostasis (proteostasis). As the loss of proteostasis by the ribosome has been identified in the other forms of TTD, here we postulate that ribosomal dysfunction is a common underlying pathomechanism of TTD.<\/jats:p>","DOI":"10.3390\/cells12141877","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T01:35:16Z","timestamp":1689644116000},"page":"1877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ribosomal Dysfunction Is a Common Pathomechanism in Different Forms of Trichothiodystrophy"],"prefix":"10.3390","volume":"12","author":[{"given":"Gaojie","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Khalid","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6091-8353","authenticated-orcid":false,"given":"Danhui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouli","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallab","family":"Maity","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4759-5254","authenticated-orcid":false,"given":"Hans A.","family":"Kestler","sequence":"additional","affiliation":[{"name":"Medical Systems Biology, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donata","family":"Orioli","sequence":"additional","affiliation":[{"name":"Istituto di Genetica Molecolare L.L. Cavalli-Sforza CNR, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Scharffetter-Kochanek","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5207-2861","authenticated-orcid":false,"given":"Sebastian","family":"Iben","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergic Diseases, Ulm University, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.dnarep.2009.10.005","article-title":"Trichothiodystrophy: From basic mechanisms to clinical implications","volume":"9","author":"Stefanini","year":"2010","journal-title":"DNA Repair"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1136\/jmg.2008.058743","article-title":"Trichothiodystrophy: A systematic review of 112 published cases char-acterises a wide spectrum of clinical manifestations","volume":"45","author":"Faghri","year":"2008","journal-title":"J. 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