{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T04:34:47Z","timestamp":1790483687538,"version":"4.1.0"},"reference-count":65,"publisher":"Cold Spring Harbor Laboratory","issue":"1","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM084065"],"award-info":[{"award-number":["GM084065"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Ohio State University Center for RNA Biology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["RNA"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Transfer RNAs acquire a variety of naturally occurring chemical modifications during their maturation; these fine-tune their structure and decoding properties in a manner critical for protein synthesis. We recently reported that in the eukaryotic parasite, <jats:italic>Trypanosoma brucei<\/jats:italic>, a methylation and deamination event are unexpectedly interconnected, whereby the tRNA adenosine deaminase (TbADAT2\/3) and the 3-methylcytosine methyltransferase (TbTrm140) strictly rely on each other for activity, leading to formation of m<jats:sup>3<\/jats:sup>C and m<jats:sup>3<\/jats:sup>U at position 32 in several tRNAs. Still however, it is not clear why these two enzymes, which work independently in other systems, are strictly codependent in <jats:italic>T. brucei<\/jats:italic>. Here, we show that these enzymes exhibit binding synergism, or a mutual increase in binding affinity, that is more than the sum of the parts, when added together in a reaction. Although these enzymes interact directly with each other, tRNA binding assays using enzyme variants mutated in critical binding and catalytic sites indicate that the observed binding synergy stems from contributions from tRNA-binding domains distal to their active sites. These results provide a rationale for the known interactions of these proteins, while also speaking to the modulation of substrate specificity between seemingly unrelated enzymes. This information should be of value in furthering our understanding of how tRNA modification enzymes act together to regulate gene expression at the post-transcriptional level and provide a basis for the interdependence of such activities.<\/jats:p>","DOI":"10.1261\/rna.062893.117","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T00:50:13Z","timestamp":1508287813000},"page":"56-66","source":"Crossref","is-referenced-by-count":10,"title":["Binding synergy as an essential step for tRNA editing and modification enzyme codependence in <i>Trypanosoma brucei<\/i>"],"prefix":"10.1261","volume":"24","author":[{"given":"Katherine M.","family":"McKenney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Anne T.","family":"Rubio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan D.","family":"Alfonzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2017,10,17]]},"reference":[{"key":"2021112106001104000_24.1.56.1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355838202024019"},{"key":"2021112106001104000_24.1.56.2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.23.3650"},{"key":"2021112106001104000_24.1.56.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090102597"},{"key":"2021112106001104000_24.1.56.4","doi-asserted-by":"publisher","DOI":"10.1261\/rna.056259.116"},{"key":"2021112106001104000_24.1.56.5","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2789"},{"key":"2021112106001104000_24.1.56.6","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0527"},{"key":"2021112106001104000_24.1.56.7","doi-asserted-by":"publisher","DOI":"10.1261\/rna.2245910"},{"key":"2021112106001104000_24.1.56.8","doi-asserted-by":"crossref","unstructured":"Bj\u00f6rk GR , Kohli J . 1990. Synthesis and function of modified nucleosides in tRNA. In Chromatography and modification of nucleosides. Part B. Biological roles and function of modification (ed. 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