{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:47:14Z","timestamp":1768513634612,"version":"3.49.0"},"posted":{"date-parts":[[2024,7,10]]},"group-title":"Genetics","reference-count":46,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The Y-linked gene\n                  <jats:italic>DDX3Y<\/jats:italic>\n                  and its X-linked homolog\n                  <jats:italic>DDX3X<\/jats:italic>\n                  survived the evolution of the human sex chromosomes from ordinary autosomes.\n                  <jats:italic>DDX3X<\/jats:italic>\n                  encodes a multi-functional RNA helicase, with mutations causing developmental disorders and cancers. We find that, among X-linked genes with surviving Y homologs,\n                  <jats:italic>DDX3X<\/jats:italic>\n                  is extraordinarily dosage-sensitive. Studying cells of individuals with sex chromosome aneuploidy, we observe that when the number of Y chromosomes increases,\n                  <jats:italic>DDX3X<\/jats:italic>\n                  transcript levels fall; conversely, when the number of X chromosomes increases,\n                  <jats:italic>DDX3Y<\/jats:italic>\n                  transcript levels fall. In 46,XY cells, CRISPRi knockdown of either\n                  <jats:italic>DDX3X<\/jats:italic>\n                  or\n                  <jats:italic>DDX3Y<\/jats:italic>\n                  causes transcript levels of the homologous gene to rise. In 46,XX cells, chemical inhibition of DDX3X protein activity elicits an increase in\n                  <jats:italic>DDX3X<\/jats:italic>\n                  transcript levels. Thus, perturbation of either\n                  <jats:italic>DDX3X<\/jats:italic>\n                  or\n                  <jats:italic>DDX3Y<\/jats:italic>\n                  expression is buffered \u2013 by negative cross-regulation of\n                  <jats:italic>DDX3X<\/jats:italic>\n                  and\n                  <jats:italic>DDX3Y<\/jats:italic>\n                  in 46,XY cells, and by negative auto-regulation of\n                  <jats:italic>DDX3X<\/jats:italic>\n                  in 46,XX cells.\n                  <jats:italic>DDX3X<\/jats:italic>\n                  -\n                  <jats:italic>DDX3Y<\/jats:italic>\n                  cross-regulation is mediated through mRNA destabilization \u2013 as shown by metabolic labeling of newly transcribed RNA \u2013 and buffers total levels of DDX3X and DDX3Y protein in human cells. We infer that post-transcriptional auto-regulation of the ancestral (autosomal)\n                  <jats:italic>DDX3<\/jats:italic>\n                  gene transmuted into auto- and cross-regulation of\n                  <jats:italic>DDX3X<\/jats:italic>\n                  and\n                  <jats:italic>DDX3Y<\/jats:italic>\n                  as these sex-linked genes evolved from ordinary alleles of their autosomal precursor.\n                <\/jats:p>","DOI":"10.1101\/2024.07.08.602613","type":"posted-content","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:25:18Z","timestamp":1720657518000},"source":"Crossref","is-referenced-by-count":2,"title":["Post-transcriptional cross- and auto-regulation buffer expression of the human RNA helicases\n                  <i>DDX3X<\/i>\n                  and\n                  <i>DDX3Y<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0102-9597","authenticated-orcid":false,"given":"Shruthi","family":"Rengarajan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Derks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-7555","authenticated-orcid":false,"given":"Daniel W.","family":"Bellott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolai","family":"Slavov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9920-3411","authenticated-orcid":false,"given":"David C.","family":"Page","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024071219450514000_2024.07.08.602613v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13206"},{"key":"2024071219450514000_2024.07.08.602613v1.2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.268516.120"},{"key":"2024071219450514000_2024.07.08.602613v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nature09172"},{"key":"2024071219450514000_2024.07.08.602613v1.4","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404368"},{"key":"2024071219450514000_2024.07.08.602613v1.5","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M113.031591"},{"key":"2024071219450514000_2024.07.08.602613v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0638-x"},{"key":"2024071219450514000_2024.07.08.602613v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01389-w"},{"key":"2024071219450514000_2024.07.08.602613v1.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1504822112"},{"key":"2024071219450514000_2024.07.08.602613v1.9","doi-asserted-by":"publisher","DOI":"10.1101\/gr.082701.108"},{"key":"2024071219450514000_2024.07.08.602613v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1186-3"},{"key":"2024071219450514000_2024.07.08.602613v1.11","doi-asserted-by":"publisher","DOI":"10.1101\/gr.261248.120"},{"key":"2024071219450514000_2024.07.08.602613v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.07.041"},{"key":"2024071219450514000_2024.07.08.602613v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/nature24277"},{"key":"2024071219450514000_2024.07.08.602613v1.14","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.19760"},{"key":"2024071219450514000_2024.07.08.602613v1.15","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.78203"},{"key":"2024071219450514000_2024.07.08.602613v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.09.009"},{"key":"2024071219450514000_2024.07.08.602613v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"2024071219450514000_2024.07.08.602613v1.18","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-018-0141-y"},{"key":"2024071219450514000_2024.07.08.602613v1.19","doi-asserted-by":"publisher","DOI":"10.1101\/gr.251421.119"},{"key":"2024071219450514000_2024.07.08.602613v1.20","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msac174"},{"key":"2024071219450514000_2024.07.08.602613v1.21","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5338.675"},{"key":"2024071219450514000_2024.07.08.602613v1.22","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5441.964"},{"key":"2024071219450514000_2024.07.08.602613v1.23","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts034"},{"key":"2024071219450514000_2024.07.08.602613v1.24","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2024071219450514000_2024.07.08.602613v1.25","doi-asserted-by":"publisher","DOI":"10.1126\/science.1228186"},{"key":"2024071219450514000_2024.07.08.602613v1.26","doi-asserted-by":"publisher","DOI":"10.1101\/gr.230433.117"},{"key":"2024071219450514000_2024.07.08.602613v1.27","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61061"},{"key":"2024071219450514000_2024.07.08.602613v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2020.05.027"},{"key":"2024071219450514000_2024.07.08.602613v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/srep15041"},{"key":"2024071219450514000_2024.07.08.602613v1.30","doi-asserted-by":"publisher","DOI":"10.2174\/092986707782023677"},{"key":"2024071219450514000_2024.07.08.602613v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2023.100259"},{"key":"2024071219450514000_2024.07.08.602613v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2023.100462"},{"key":"2024071219450514000_2024.07.08.602613v1.33","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.11.1985"},{"key":"2024071219450514000_2024.07.08.602613v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.07.005"},{"key":"2024071219450514000_2024.07.08.602613v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.10.008"},{"key":"2024071219450514000_2024.07.08.602613v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.04.022"},{"key":"2024071219450514000_2024.07.08.602613v1.37","unstructured":"Silvia 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A synthetic approach to study function and expression of the Saccharomyces cerevisiae RNA helicase Ded1. Doctor of Sciences Thesis. 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