{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:24:03Z","timestamp":1772159043535,"version":"3.50.1"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["GM134021"],"award-info":[{"award-number":["GM134021"]}]},{"name":"HHS | National Institutes of Health","award":["R35-GM126945"],"award-info":[{"award-number":["R35-GM126945"]}]},{"name":"HHS | NIH | National Cancer Institute","award":["P30 CA08748"],"award-info":[{"award-number":["P30 CA08748"]}]},{"name":"National Science Foundation","award":["1746057"],"award-info":[{"award-number":["1746057"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,2,14]]},"abstract":"<jats:p>\n            The inositol pyrophosphate metabolite 1,5-IP\n            <jats:sub>8<\/jats:sub>\n            governs repression of fission yeast phosphate homeostasis genes\n            <jats:italic>pho1<\/jats:italic>\n            ,\n            <jats:italic>pho84<\/jats:italic>\n            , and\n            <jats:italic>tgp1<\/jats:italic>\n            by lncRNA-mediated transcriptional interference. Asp1 pyrophosphatase mutations that increase IP\n            <jats:sub>8<\/jats:sub>\n            levels elicit precocious lncRNA termination, leading to derepression of the\n            <jats:italic>PHO<\/jats:italic>\n            genes. Deletions of the Asp1 pyrophosphatase domain result in growth impairment or lethality via IP\n            <jats:sub>8<\/jats:sub>\n            agonism of transcription termination. It was assumed that IP\n            <jats:sub>8<\/jats:sub>\n            toxicity ensues from dysregulation of essential genes. In this study, a suppressor screen revealed that IP\n            <jats:sub>8<\/jats:sub>\n            toxicosis of Asp1 pyrophosphatase mutants is caused by: (i) a &gt;40-fold increase in the expression of the inessential\n            <jats:italic>tgp1<\/jats:italic>\n            gene encoding a glycerophosphodiester transporter and (ii) the presence of glycerophosphocholine in the growth medium. The suppressor screen yielded missense mutations in two upstream enzymes of inositol polyphosphate metabolism: the phospholipase C enzyme Plc1 that generates IP\n            <jats:sub>3<\/jats:sub>\n            and the essential Kcs1 kinase that converts IP\n            <jats:sub>6<\/jats:sub>\n            to 5-IP\n            <jats:sub>7<\/jats:sub>\n            , the immediate precursor of IP\n            <jats:sub>8<\/jats:sub>\n            .\n          <\/jats:p>","DOI":"10.1128\/mbio.03062-23","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T14:00:20Z","timestamp":1703253620000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Genetic suppressor screen identifies Tgp1 (glycerophosphocholine transporter), Kcs1 (IP\n            <sub>6<\/sub>\n            kinase), and Plc1 (phospholipase C) as determinants of inositol pyrophosphate toxicosis in fission yeast"],"prefix":"10.1128","volume":"15","author":[{"given":"Lauren","family":"Bednor","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medical College, New York, USA"},{"name":"Molecular Biology Program, Sloan-Kettering Institute, New York, USA"},{"name":"Weill Cornell Graduate School of Medical Sciences, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana M.","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Molecular Biology Program, Sloan-Kettering Institute, New York, USA"},{"name":"Gerstner Sloan Kettering Graduate School of Biomedical Sciences, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angad","family":"Garg","sequence":"additional","affiliation":[{"name":"Molecular Biology Program, Sloan-Kettering Institute, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stewart","family":"Shuman","sequence":"additional","affiliation":[{"name":"Molecular Biology Program, Sloan-Kettering Institute, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3824-9819","authenticated-orcid":false,"given":"Beate","family":"Schwer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medical College, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00047-18"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908875117"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01034-22"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03087-22"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21735"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz567"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa630"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1810711115"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.078682.121"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa776"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03476-21"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad9858"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2017.08.012"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad063"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1263"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2020.101065"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.17912\/micropub.biology.000399"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.320110209"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst025225s"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5178"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/149.4.1707"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507051200"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2006.04.013"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05160-11"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.505735"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-13-697"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403648200"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6576"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1261\/rna.063966.117"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00315789"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr509"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321842111"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03062-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03062-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,11]],"date-time":"2024-08-11T18:31:02Z","timestamp":1723401062000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.03062-23"}},"subtitle":[],"editor":[{"given":"Fred M.","family":"Winston","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,14]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,14]]}},"alternative-id":["10.1128\/mbio.03062-23"],"URL":"https:\/\/doi.org\/10.1128\/mbio.03062-23","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,14]]},"assertion":[{"value":"2023-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03062-23"}}