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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,16]]},"abstract":"<jats:p>\n                    The virulence of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    , which causes the deadliest form of human malaria, is attributed to its ability to evade the human immune response. These parasites \u201cchoose\u201d to express a single variant from a repertoire of surface antigens called PfEMP1, which are placed on the surface of the infected red cell. Immune evasion is achieved by switches in expression between\n                    <jats:italic>var<\/jats:italic>\n                    genes, each encoding a different\n                    <jats:italic>Pf<\/jats:italic>\n                    EMP1 variant. While the mechanisms that regulate mutually exclusive expression of\n                    <jats:italic>var<\/jats:italic>\n                    genes are still elusive, antisense long-noncoding RNAs (lncRNAs) transcribed from the intron of the active\n                    <jats:italic>var<\/jats:italic>\n                    gene were implicated in the \u201cchoice\u201d of the single active\n                    <jats:italic>var<\/jats:italic>\n                    gene. Here, we show that this lncRNA colocalizes with the site of\n                    <jats:italic>var<\/jats:italic>\n                    mRNA transcription and is anchored to the\n                    <jats:italic>var<\/jats:italic>\n                    locus via DNA:RNA interactions. We define the\n                    <jats:italic>var<\/jats:italic>\n                    lncRNA interactome and identify a redox sensor,\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    thioredoxin peroxidase I (\n                    <jats:italic>Pf<\/jats:italic>\n                    TPx-1), as one of the proteins associated with the\n                    <jats:italic>var<\/jats:italic>\n                    antisense lncRNA. We show that\n                    <jats:italic>Pf<\/jats:italic>\n                    TPx-1 localizes to a nuclear subcompartment associated with active transcription on the nuclear periphery, in ring-stage parasite, when\n                    <jats:italic>var<\/jats:italic>\n                    transcription occurs. In addition,\n                    <jats:italic>Pf<\/jats:italic>\n                    TPx-1 colocalizes with S-adenosylmethionine synthetase (\n                    <jats:italic>Pf<\/jats:italic>\n                    SAMS) in the nucleus, and its overexpression leads to activation of\n                    <jats:italic>var2csa,<\/jats:italic>\n                    similar to overexpression of\n                    <jats:italic>Pf<\/jats:italic>\n                    SAMS. Furthermore, we show that\n                    <jats:italic>Pf<\/jats:italic>\n                    TPx-1 knockdown alters the\n                    <jats:italic>var<\/jats:italic>\n                    switch rate as well as activation of additional gene subsets. Taken together, our data indicate that nuclear\n                    <jats:italic>Pf<\/jats:italic>\n                    TPx-1 plays a role in gene activation possibly by providing a redox-controlled nuclear microenvironment ideal for active transcription.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2201247119","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T15:16:07Z","timestamp":1659971767000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":18,"title":["A nuclear redox sensor modulates gene activation and\n                    <i>var<\/i>\n                    switching in\n                    <i>Plasmodium falciparum<\/i>"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6123-448X","authenticated-orcid":false,"given":"Adina","family":"Heinberg","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, Institute for Medical Research Israel\u2013Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbar","family":"Amit-Avraham","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, Institute for Medical Research Israel\u2013Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1818-3592","authenticated-orcid":false,"given":"Vera","family":"Mitesser","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, Institute for Medical Research Israel\u2013Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4519-2424","authenticated-orcid":false,"given":"Karina","family":"Simantov","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, Institute for Medical Research Israel\u2013Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2383-5409","authenticated-orcid":false,"given":"Manish","family":"Goyal","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, Institute for Medical Research Israel\u2013Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Nevo","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, Info-CORE, Hebrew University of Jerusalem and Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Kandelis-Shalev","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, Institute for Medical Research Israel\u2013Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, Institute for Medical Research Israel\u2013Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7878-1650","authenticated-orcid":false,"given":"Ron","family":"Dzikowski","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, Institute for Medical Research Israel\u2013Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"(WHO) World Malaria Report 2020 (2020). https:\/\/www.who.int\/publications\/i\/item\/9789240015791. 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