{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:51:46Z","timestamp":1790628706504,"version":"4.1.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["APP1165354"],"award-info":[{"award-number":["APP1165354"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2023,8,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Nonsense-mediated decay (NMD) is a conserved mRNA quality control process that eliminates transcripts bearing a premature termination codon. In addition to its role in removing erroneous transcripts, NMD is involved in post-transcriptional regulation of gene expression via programmed intron retention in metazoans. The apicomplexan parasite\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    shows relatively high levels of intron retention, but it is unclear whether these variant transcripts are functional targets of NMD. In this study, we use CRISPR-Cas9 to disrupt and epitope-tag the\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    orthologs of two core NMD components:\n                    <jats:italic>Pf<\/jats:italic>\n                    UPF1 (PF3D7_1005500) and\n                    <jats:italic>Pf<\/jats:italic>\n                    UPF2 (PF3D7_0925800). We localize both\n                    <jats:italic>Pf<\/jats:italic>\n                    UPF1 and\n                    <jats:italic>Pf<\/jats:italic>\n                    UPF2 to puncta within the parasite cytoplasm and show that these proteins interact with each other and other mRNA-binding proteins. Using RNA-seq, we find that although these core NMD orthologs are expressed and interact in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    , they are not required for degradation of nonsense transcripts. Furthermore, our work suggests that the majority of intron retention in\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    has no functional role and that NMD is not required for parasite growth\n                    <jats:italic>ex vivo<\/jats:italic>\n                    .\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>In many organisms, the process of destroying nonsense transcripts is dependent on a small set of highly conserved proteins. We show that in the malaria parasite, these proteins do not impact the abundance of nonsense transcripts. Furthermore, we demonstrate efficient CRISPR-Cas9 editing of the malaria parasite using commercial Cas9 nuclease and synthetic guide RNA, streamlining genomic modifications in this genetically intractable organism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00233-23","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T09:00:36Z","timestamp":1687856436000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Nonsense-mediated decay machinery in\n                    <i>Plasmodium falciparum<\/i>\n                    is inefficient and non-essential"],"prefix":"10.1128","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0278-4171","authenticated-orcid":true,"given":"Emma","family":"McHugh","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne , Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela S.","family":"Bulloch","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne , Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Batinovic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Microbiology, La Trobe University , Bundoora, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron J.","family":"Patrick","sequence":"additional","affiliation":[{"name":"School of Mathematics and Statistics, The University of Melbourne , Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drishti K.","family":"Sarna","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne , Parkville, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0114-7808","authenticated-orcid":true,"given":"Stuart A.","family":"Ralph","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne , Parkville, Victoria, 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