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Management of candidemia relies on a few antifungal agents, with fluconazole being first line therapy. The emergence of fluconazole-resistant strains highlights the pressing need to improve our molecular understanding of the drug response mechanisms. By sequencing the 5\u2019P mRNA degradation intermediates, we establish that co-translational mRNA decay occurs in <jats:italic>C. albicans<\/jats:italic> and characterize how in vivo 5\u00b4-3\u00b4 exonuclease degradation trails the last translating ribosome. Thus, the study of the 5\u2019 Phosphorylated mRNA degradome (5PSeq) offers a simple and affordable way to measure ribosome dynamics and identify codon specific ribosome stalls in response to drugs and amino acid deprivation. Building upon this, we combine RNA-Seq and 5PSeq to study the early response of sensitive and resistant <jats:italic>C. albicans<\/jats:italic> isolates to fluconazole. Our results highlight that transcriptional responses, rather than changes in ribosome dynamics, are the main driver of <jats:italic>Candida<\/jats:italic> resistance to fluconazole.<\/jats:p>","DOI":"10.1038\/s41598-024-80435-w","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T16:29:26Z","timestamp":1732292966000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The early transcriptional and post-transcriptional responses to fluconazole in sensitive and resistant Candida albicans"],"prefix":"10.1038","volume":"14","author":[{"given":"Irene","family":"Stevens","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fitz Gerald","family":"Silao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Huch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kicki","family":"Ryman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Carvajal-Jimenez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per O.","family":"Ljungdahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicent","family":"Pelechano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"80435_CR1","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1111\/myc.12981","volume":"62","author":"V \u00d6zenci","year":"2019","unstructured":"\u00d6zenci, V. et al. 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