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One well-characterised USE in the 3'UTR of the\u00a0Drosophila polo gene affects adult fly phenotypes when disrupted. We have now identified a highly conserved sequence within this USE (DplUSE) in the 3'UTR of several vertebrate genes, including in zebrafish, mouse, and human genomes and show that DplUSE enhances gene expression in human cells and zebrafish embryos. We show that, in humans, DplUSE-containing genes are associated with congenital disease processes, and that disruption of DplUSE function impairs zebrafish development. We also found that HuR\/ELAVL1, hnRNPC, and PTBP1\/hnRNPI bind to\u00a0DplUSE RNA and are required for its activity in a human cell line, suggesting a highly conserved mechanism across distantly related species. Our results indicate that PTBP1 has a global function in alternative polyadenylation, activating the selection of distal polyA sites and repressing intronic polyadenylation in DplUSE-containing genes while hnRNPC and HuR modulate their expression. Additionally, we found that a colon cancer-associated SNP in the POU2AF2\/C11orf53 3'UTR creates an ectopic DplUSE site, increasing gene expression in zebrafish gut cells and in a human cell line. We have therefore identified a short 3'UTR motif present in diverse vertebrate genes that controls their expression through conserved RBPs interactions and is implicated in human disease.<\/jats:p>","DOI":"10.1093\/nar\/gkaf1340","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T12:33:24Z","timestamp":1763382804000},"source":"Crossref","is-referenced-by-count":0,"title":["A conserved 3\u2032UTR short motif regulates gene expression in vertebrates"],"prefix":"10.1093","volume":"54","author":[{"given":"Ana","family":"Eufr\u00e1sio","sequence":"first","affiliation":[{"name":"Vertebrate Development and Regeneration Group, i3S - Universidade do Porto, 4200-135, Porto, Portugal"},{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135, Porto ,","place":["Portugal"]},{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135, Porto ,","place":["Portugal"]},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto - Programa Doutoral em Biologia Molecular e Celular, 4050-313, Porto ,","place":["Portugal"]}]},{"given":"Joana","family":"Machado","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135, Porto ,","place":["Portugal"]},{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135, Porto ,","place":["Portugal"]},{"name":"Gene Regulation Group, i3S - Universidade do Porto, 4200-135, Porto, Portugal"},{"name":"Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade de Lisboa , 1749-016, Lisboa ,","place":["Portugal"]}]},{"given":"Joana","family":"Azevedo","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, 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Portugal"}]},{"given":"Filipe","family":"Henriques","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135, Porto ,","place":["Portugal"]},{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135, Porto ,","place":["Portugal"]},{"name":"Gene Regulation Group, i3S - Universidade do Porto, 4200-135, Porto, Portugal"}]},{"given":"Ana","family":"Jesus","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135, Porto ,","place":["Portugal"]},{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135, Porto ,","place":["Portugal"]},{"name":"Gene Regulation Group, i3S - Universidade do Porto, 4200-135, Porto, 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