{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:27:43Z","timestamp":1790018863519,"version":"4.0.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T00:00:00Z","timestamp":1633305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["19-34-51047"],"award-info":[{"award-number":["19-34-51047"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Russian Ministry of Science and Higher Education"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Saccharomyces\u00a0cerevisiae gene deletion collection is widely used for functional gene annotation and genetic interaction analyses. However, the standard G418-resistance cassette used to produce knockout mutants delivers strong regulatory elements into the target genetic loci. To date, its side effects on the expression of neighboring genes have never been systematically assessed. Here, using ribosome profiling data, RT-qPCR, and reporter expression, we investigated perturbations induced by the KanMX module. Our analysis revealed significant alterations in the transcription efficiency of neighboring genes and, more importantly, severe impairment of their mRNA translation, leading to changes in protein abundance. In the \u2018head-to-head\u2019 orientation of the deleted and neighboring genes, knockout often led to a shift of the transcription start site of the latter, introducing new uAUG codon(s) into the expanded 5\u2032 untranslated region (5\u2032 UTR). In the \u2018tail-to-tail\u2019 arrangement, knockout led to activation of alternative polyadenylation signals in the neighboring gene, thus altering its 3\u2032 UTR. These events may explain the so-called neighboring gene effect (NGE), i.e. false genetic interactions of the deleted genes. We estimate that in as much as \u223c1\/5 of knockout strains the expression of neighboring genes may be substantially (&amp;gt;2-fold) deregulated at the level of translation.<\/jats:p>","DOI":"10.1093\/nar\/gkab872","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T23:14:23Z","timestamp":1631747663000},"page":"11134-11144","source":"Crossref","is-referenced-by-count":19,"title":["A standard knockout procedure alters expression of adjacent loci at the translational level"],"prefix":"10.1093","volume":"49","author":[{"given":"Artyom A","family":"Egorov","sequence":"first","affiliation":[{"name":"Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology (State University), Dolgoprudny\u00a0141700, Russia"},{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"},{"name":"Sirius University of Science and Technology, 1 Olympic Ave, Sochi\u00a0354340, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander I","family":"Alexandrov","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"},{"name":"FRC of Biotechnology of the Russian Academy of Sciences, Bach Institute of Biochemistry, Moscow\u00a0119071, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery\u00a0N","family":"Urakov","sequence":"additional","affiliation":[{"name":"FRC of Biotechnology of the Russian Academy of Sciences, Bach Institute of Biochemistry, Moscow\u00a0119071, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desislava\u00a0S","family":"Makeeva","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"},{"name":"Sirius University of Science and Technology, 1 Olympic Ave, Sochi\u00a0354340, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman\u00a0O","family":"Edakin","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"},{"name":"Sirius University of Science and Technology, 1 Olympic Ave, Sochi\u00a0354340, Russia"},{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5982-4405","authenticated-orcid":false,"given":"Artem S","family":"Kushchenko","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"},{"name":"Sirius University of Science and Technology, 1 Olympic Ave, Sochi\u00a0354340, Russia"},{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0372-7016","authenticated-orcid":false,"given":"Vadim\u00a0N","family":"Gladyshev","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan\u00a0V","family":"Kulakovskiy","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"},{"name":"Sirius University of Science and Technology, 1 Olympic Ave, Sochi\u00a0354340, Russia"},{"name":"Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow\u00a0119991, Russia"},{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow\u00a0119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1774-8475","authenticated-orcid":false,"given":"Sergey\u00a0E","family":"Dmitriev","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"},{"name":"Sirius University of Science and Technology, 1 Olympic Ave, Sochi\u00a0354340, Russia"},{"name":"Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow\u00a0119234, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,10,4]]},"reference":[{"key":"2021110312550967800_B1","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1126\/science.274.5287.546","article-title":"Life with 6000 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cerevisiae","volume":"10","author":"Wach","year":"1994","journal-title":"Yeast"},{"key":"2021110312550967800_B5"},{"key":"2021110312550967800_B6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1534\/genetics.114.161620","article-title":"The yeast deletion collection: a decade of functional genomics","volume":"197","author":"Giaever","year":"2014","journal-title":"Genetics"},{"key":"2021110312550967800_B7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.cell.2019.01.033","article-title":"Global genetic networks and the genotype-to-phenotype relationship","volume":"177","author":"Costanzo","year":"2019","journal-title":"Cell"},{"key":"2021110312550967800_B8","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.tig.2005.11.003","article-title":"Global synthetic-lethality analysis and yeast functional profiling","volume":"22","author":"Ooi","year":"2006","journal-title":"Trends 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Genet."},{"key":"2021110312550967800_B42","doi-asserted-by":"crossref","first-page":"D700","DOI":"10.1093\/nar\/gkr1029","article-title":"Saccharomyces Genome Database: the genomics resource of budding yeast","volume":"40","author":"Cherry","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2021110312550967800_B43","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.gde.2012.12.004","article-title":"Regulation and dysregulation of 3'UTR-mediated translational control","volume":"23","author":"Jia","year":"2013","journal-title":"Curr. Opin. Genet. 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Perspect Biol."},{"key":"2021110312550967800_B46","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/nar\/gkw1190","article-title":"Insights into the mechanisms of eukaryotic translation gained with ribosome profiling","volume":"45","author":"Andreev","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2021110312550967800_B47","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1126\/science.1215110","article-title":"High-resolution view of the yeast meiotic program revealed by ribosome profiling","volume":"335","author":"Brar","year":"2012","journal-title":"Science"},{"key":"2021110312550967800_B48","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1534\/g3.112.003640","article-title":"Extensive transcript diversity and novel upstream open reading frame regulation in yeast","volume":"3","author":"Waern","year":"2013","journal-title":"G3"},{"key":"2021110312550967800_B49","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.cell.2018.01.035","article-title":"Pervasive, coordinated protein-level changes driven by transcript isoform switching during meiosis","volume":"172","author":"Cheng","year":"2018","journal-title":"Cell"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/19\/11134\/41071451\/gkab872.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/19\/11134\/41071451\/gkab872.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T08:56:01Z","timestamp":1635929761000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/49\/19\/11134\/6381141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,4]]},"references-count":49,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2021,10,4]]},"published-print":{"date-parts":[[2021,11,8]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkab872","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.08.21.457210","asserted-by":"object"}]},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,8]]},"published":{"date-parts":[[2021,10,4]]}}}