{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:29:47Z","timestamp":1787009387014,"version":"build-2736575974"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2019,5,25]],"date-time":"2019-05-25T00:00:00Z","timestamp":1558742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["100320\/Z\/12\/Z"],"award-info":[{"award-number":["100320\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203134\/Z\/16\/Z"],"award-info":[{"award-number":["203134\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["097418\/Z\/11\/Z"],"award-info":[{"award-number":["097418\/Z\/11\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Post-transcriptional regulons coordinate the expression of groups of genes in eukaryotic cells, yet relatively few have been characterized. Parasitic trypanosomatids are particularly good models for studies on such mechanisms because they exhibit almost exclusive polycistronic, and unregulated, transcription. Here, we identify the Trypanosoma brucei ZC3H39\/40 RNA-binding proteins as regulators of the respiratome; the mitochondrial electron transport chain (complexes I\u2013IV) and the FoF1-ATP synthase (complex V). A high-throughput RNAi screen initially implicated both ZC3H proteins in variant surface glycoprotein (VSG) gene silencing. This link was confirmed and both proteins were shown to form a cytoplasmic ZC3H39\/40 complex. Transcriptome and mRNA-interactome analyses indicated that the impact on VSG silencing was indirect, while the ZC3H39\/40 complex specifically bound and stabilized transcripts encoding respiratome-complexes. Quantitative proteomic analyses revealed specific positive control of &gt;20 components from complexes I, II and V. Our findings establish a link between the mitochondrial respiratome and VSG gene silencing in bloodstream form T. brucei. They also reveal a major respiratome regulon controlled by the conserved trypanosomatid ZC3H39\/40 RNA-binding proteins.<\/jats:p>","DOI":"10.1093\/nar\/gkz455","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T15:21:11Z","timestamp":1557501671000},"page":"7063-7077","source":"Crossref","is-referenced-by-count":26,"title":["A post-transcriptional respiratome regulon in trypanosomes"],"prefix":"10.1093","volume":"47","author":[{"given":"Anna","family":"Trenaman","sequence":"first","affiliation":[{"name":"The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-6890","authenticated-orcid":false,"given":"Lucy","family":"Glover","sequence":"additional","affiliation":[{"name":"The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5173-9284","authenticated-orcid":false,"given":"David","family":"Horn","sequence":"additional","affiliation":[{"name":"The Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,25]]},"reference":[{"key":"2019072309503135100_B1","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/S1097-2765(02)00559-2","article-title":"Eukaryotic mRNPs may represent posttranscriptional operons","volume":"9","author":"Keene","year":"2002","journal-title":"Mol. 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Microbiol."},{"key":"2019072309503135100_B5","first-page":"436","article-title":"The genome of the kinetoplastid parasite","volume":"309","author":"Ivens","year":"2005","journal-title":"Leishmania major Sci."},{"key":"2019072309503135100_B6","doi-asserted-by":"crossref","first-page":"e32467","DOI":"10.7554\/eLife.32467","article-title":"Codon choice directs constitutive mRNA levels in trypanosomes","volume":"7","author":"de\u00a0Freitas\u00a0Nascimento","year":"2018","journal-title":"Elife"},{"key":"2019072309503135100_B7","doi-asserted-by":"crossref","first-page":"e32496","DOI":"10.7554\/eLife.32496","article-title":"Codon usage bias controls mRNA and protein abundance in trypanosomatids","volume":"7","author":"Jeacock","year":"2018","journal-title":"Elife"},{"key":"2019072309503135100_B8","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/cmi.12268","article-title":"The emerging role of RNA-binding proteins in the life cycle of Trypanosoma brucei","volume":"16","author":"Kolev","year":"2014","journal-title":"Cell Microbiol."},{"key":"2019072309503135100_B9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pt.2010.06.011","article-title":"Trans-acting proteins regulating mRNA maturation, stability and translation in trypanosomatids","volume":"27","author":"Kramer","year":"2011","journal-title":"Trends Parasitol."},{"key":"2019072309503135100_B10","doi-asserted-by":"crossref","first-page":"8591","DOI":"10.1093\/nar\/gkt647","article-title":"Global identification of conserved post-transcriptional regulatory programs in trypanosomatids","volume":"41","author":"Najafabadi","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2019072309503135100_B11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0166-6851(95)02503-0","article-title":"Role of 3\u2032-untranslated regions in the regulation of hexose transporter mRNAs in Trypanosoma brucei","volume":"75","author":"Hotz","year":"1995","journal-title":"Mol. 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Parasitol."},{"key":"2019072309503135100_B12","doi-asserted-by":"crossref","first-page":"5312","DOI":"10.1093\/nar\/gkl598","article-title":"Post-transcriptional control of nuclear-encoded cytochrome oxidase subunits in Trypanosoma brucei: evidence for genome-wide conservation of life-cycle stage-specific regulatory elements","volume":"34","author":"Mayho","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2019072309503135100_B13","doi-asserted-by":"crossref","first-page":"7705","DOI":"10.1093\/nar\/gks533","article-title":"Identification of the regulatory elements controlling the transmission stage-specific gene expression of PAD1 in Trypanosoma brucei","volume":"40","author":"MacGregor","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2019072309503135100_B14","doi-asserted-by":"crossref","first-page":"jcs.206417","DOI":"10.1242\/jcs.206417","article-title":"Distinct 3\u2032 UTRs regulate the life-cycle-specific expression of two TCTP paralogs in Trypanosoma brucei","volume":"131","author":"Jojic","year":"2018","journal-title":"J. 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