{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T06:54:34Z","timestamp":1776322474811,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n Plasmodium falciparum<\/jats:italic>\n , the causative agent of severe malaria, predominantly reproduces through asexual stages within human red blood cells, with a small subset differentiating into transmissible gametocytes. TCF25 is recognized in other eukaryotes as a protein with dual roles: a transcriptional regulator and a key component of the Ribosome-associated Quality Control (RQC) complex. Nevertheless, the precise biological function of TCF25 in\n Plasmodium<\/jats:italic>\n spp. remains inadequately elucidated.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n To investigate the function of TCF25, we created a\n tcf25<\/jats:italic>\n knockout (\n tcf25_ko<\/jats:italic>\n ) parasite strain and conducted comparative transcriptomic analysis during the ring and schizont stages. Gametocyte induction experiments were performed to investigate the impact of\n tcf25<\/jats:italic>\n deletion on gametocyte development. Chromatin immunoprecipitation sequencing (ChIP-seq) was utilized to delineate the genome-wide binding profiles in schizont-stage parasites. Additionally, RT\u2013qPCR was used to quantify changes in rRNA expression levels after\n tcf25<\/jats:italic>\n knockout.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Transcriptomic analysis of\n tcf25_ko<\/jats:italic>\n parasites indicated substantial dysregulation, with 168 genes downregulated and 24 genes upregulated during the ring stage, and 53 genes downregulated and 4 genes upregulated during the schizont stage. ChIP-seq analysis identified 44 high-confidence TCF25-binding target genes, which notably included the rDNA. Furthermore, TCF25 deficiency resulted in upregulated rRNA expression, particularly affecting 28S rRNA, a core component of the 60S ribosomal subunit.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n This study identifies TCF25 as a key regulator of various biological processes in\n P. falciparum<\/jats:italic>\n . It is shown that TCF25 plays a crucial role in gametocytogenesis by influencing the\n ap2-g<\/jats:italic>\n pathway. Additionally, a novel function of TCF25 in ribosomal biogenesis is uncovered, wherein it directly controls A-type rRNAs expression and ribosomal subunit homeostasis. These discoveries offer fresh perspectives on the molecular mechanisms that oversee transmission and ribosome biogenesis in malaria parasites.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1652542","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T05:26:50Z","timestamp":1761283610000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Transcription factor 25 modulates gametocytogenesis and ribosome biogenesis in the malaria parasite Plasmodium falciparum"],"prefix":"10.3389","volume":"15","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandara","family":"Ngim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingru","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingfeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Shang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1101\/gad.352389.124","article-title":"The ribosome-associated quality control factor TCF25 imposes K48 specificity on Listerin-mediated ubiquitination of nascent chains by binding and specifically orienting the acceptor ubiquitin","volume":"39","author":"Abaeva","year":"2025","journal-title":"Genes Dev."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100586","article-title":"Rqc1 and other yeast proteins containing highly positively charged sequences are not targets of the RQC complex","volume":"296","author":"Barros","year":"2021","journal-title":"J. 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