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Previously, we reported a malaria parasite protein kinase,\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      CLK3, as a target offering a cure, prophylaxis, and transmission blocking. The homology between\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      CLK3 and human kinases suggested that the mechanism of parasiticidal activity of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      CLK3 inhibitors is disruption of RNA processing. Here, we use RNA sequencing to reveal that selective\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      CLK3 inhibition extensively affects RNA splicing with 2,039 splice-junctions across 1,125 genes mis-spliced in treated wild-type parasites compared to controls. The function of mis-spliced transcripts showed that the affected genes were involved in numerous essential parasite processes associated with multiple life cycle stages and revealed transcripts and introns particularly susceptible to inhibition. Our study supports the role of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      CLK3 as an important regulator of spliceosome activity and establishes the distinct mechanism of parasiticidal activity of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      CLK3 inhibitors from current front-line treatments.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01561-25","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:00:44Z","timestamp":1782129644000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of PfCLK3 interferes with malaria parasite RNA splicing and explains the mechanism of action of a new class of antimalarial candidates"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9121-2396","authenticated-orcid":true,"given":"Omar","family":"Janha","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"Keltic Pharma Therapeutics Limited, Advanced Research Centre, University of Glasgow","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niniola","family":"Olaniyan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Molecular Biosciences, Advanced Research Centre, University of Glasgow","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1782-2775","authenticated-orcid":true,"given":"Go Ka","family":"Diam","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02e7b5302","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences, Nanyang Technological University","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saumya","family":"Sharma","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"Keltic Pharma Therapeutics Limited, Advanced Research Centre, University of Glasgow","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-5212","authenticated-orcid":true,"given":"Dario","family":"Beraldi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of infection and Immunity, College of Medical, Veterinary and Life Science, University of Glasgow","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1726-7353","authenticated-orcid":true,"given":"Andrew G.","family":"Jamieson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Chemistry Advanced Research Centre, University of Glasgow","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbynek","family":"Bozdech","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02e7b5302","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences, Nanyang Technological University","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1807-3123","authenticated-orcid":true,"given":"Andrew B.","family":"Tobin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Molecular Biosciences, Advanced Research Centre, University of Glasgow","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0877-3564","authenticated-orcid":true,"given":"Katarzyna","family":"Modrzynska","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00vtgdb53","id-type":"ROR","asserted-by":"publisher"}],"name":"School of infection and Immunity, College of Medical, Veterinary and Life Science, University of Glasgow","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","unstructured":"Worl. 2025. 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