{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:23:36Z","timestamp":1770337416497,"version":"3.49.0"},"posted":{"date-parts":[[2026,1,27]]},"group-title":"Microbiology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["217105\/Z\/19\/Z"],"award-info":[{"award-number":["217105\/Z\/19\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Like other cells, parasitic and other trypanosomatids sense and regulate Zn\n                  <jats:sup>2+<\/jats:sup>\n                  transport, but the mechanisms involved remained unknown. Here we identify a trypanosome RNA-binding protein which specifically eliminates ZIP3 Zn\n                  <jats:sup>2+<\/jats:sup>\n                  -transporter mRNA in Zn\n                  <jats:sup>2+<\/jats:sup>\n                  -replete conditions. We first demonstrated that\n                  <jats:italic>Trypanosoma brucei ZIP3<\/jats:italic>\n                  mRNA abundance is subject to 3\u2019-untranslated region (3\u2019-UTR) and Zn\n                  <jats:sup>2+<\/jats:sup>\n                  -dependent negative control. A genome-wide RNA interference library screen, using a reporter associated with the\n                  <jats:italic>ZIP3<\/jats:italic>\n                  3\u2019-UTR, identified Tb927.11.9510 as a candidate Zn\n                  <jats:sup>2+<\/jats:sup>\n                  -sensor. We name this protein Zinc Nuclear Knuckles 1 (ZNK1) since it localises to the nucleus and contains several Zn\n                  <jats:sup>2+<\/jats:sup>\n                  -knuckle motifs. ZNK1 is conserved among trypanosomatids, and a PIN-domain suggests a ribonuclease-based mechanism. We validate ZNK1 as a\n                  <jats:italic>ZIP3<\/jats:italic>\n                  3\u2019-UTR dependent negative regulator and identify a GU-repeat motif in the\n                  <jats:italic>ZIP3<\/jats:italic>\n                  3\u2019-UTR that is predictive of negative control by ZNK1. We use Cas9-editing to knockout ZNK1, and RNA-seq to assess the consequences, revealing highly specific accumulation of\n                  <jats:italic>ZIP3<\/jats:italic>\n                  transcripts in\n                  <jats:italic>znk1<\/jats:italic>\n                  -null cells. We conclude that ZNK1 senses Zn\n                  <jats:sup>2+<\/jats:sup>\n                  -abundance and eliminates ZIP3 mRNA in a Zn\n                  <jats:sup>2+<\/jats:sup>\n                  -dependent manner. We suggest that trypanosomatid ZNK1 is an RNA-specific zinc finger nuclease that binds\n                  <jats:italic>ZIP3<\/jats:italic>\n                  3\u2019-UTRs and degrades\n                  <jats:italic>ZIP3<\/jats:italic>\n                  mRNA only when the tandem sensor modules are coordinated with Zn\n                  <jats:sup>2+<\/jats:sup>\n                  .\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Key points<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Trypanosome Zinc Nuclear Knuckles 1 (ZNK1) is a zinc-sensor that eliminates zinc transporter mRNA.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>ZNK1 negative control operates via the transporter mRNA 3\u2019-untranslated region.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>The findings indicate that trypanosomatid ZNK1 is a conserved RNA-specific zinc finger nuclease.<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.27.702079","type":"posted-content","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T03:25:21Z","timestamp":1769570721000},"source":"Crossref","is-referenced-by-count":0,"title":["ZNK1 senses zinc and degrades zinc transporter mRNA in trypanosomes"],"prefix":"10.64898","author":[{"given":"Teresa","family":"Le\u00e3o","sequence":"first","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal"},{"name":"Faculty of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK"}]},{"given":"Anna","family":"Trenaman","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0051-017X","authenticated-orcid":false,"given":"Michele","family":"Tinti","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK"}]},{"given":"Gustavo Bravo","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK"}]},{"given":"Id\u00e1lio J.","family":"Viegas","sequence":"additional","affiliation":[{"name":"iMM \u2013 Instituto de Medicina Molecular, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5752-6586","authenticated-orcid":false,"given":"Luisa M.","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"iMM \u2013 Instituto de Medicina Molecular, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028, Lisboa, Portugal"}]},{"given":"Margarida","family":"Duarte","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal"}]},{"given":"Ana Maria","family":"Tom\u00e1s","sequence":"additional","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5173-9284","authenticated-orcid":false,"given":"David","family":"Horn","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK"}]}],"member":"54368","reference":[{"key":"2026020503500949000_2026.01.27.702079v1.1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.190072"},{"key":"2026020503500949000_2026.01.27.702079v1.2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.07368-11"},{"key":"2026020503500949000_2026.01.27.702079v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3028"},{"key":"2026020503500949000_2026.01.27.702079v1.4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.588814"},{"key":"2026020503500949000_2026.01.27.702079v1.5","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00035.2014"},{"key":"2026020503500949000_2026.01.27.702079v1.6","doi-asserted-by":"crossref","unstructured":"Eide, D.J. 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