{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:22:57Z","timestamp":1789176177410,"version":"build-2803163510"},"reference-count":45,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM132087"],"award-info":[{"award-number":["GM132087"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA120964"],"award-info":[{"award-number":["CA120964"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["P01CA120964"],"award-info":[{"award-number":["P01CA120964"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,4,9]]},"abstract":"<jats:p>\n                    Loss-of-function and gain-of-function genetic perturbations provide valuable insights into gene function. In\n                    <jats:italic>Drosophila<\/jats:italic>\n                    cells, while genome-wide loss-of-function screens have been extensively used to reveal mechanisms of a variety of biological processes, approaches for performing genome-wide gain-of-function screens are still lacking. Here, we describe a pooled CRISPR activation (CRISPRa) screening platform in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    cells and apply this method to both focused and genome-wide screens to identify rapamycin resistance genes. The screens identified three genes as novel rapamycin resistance genes: a member of the SLC16 family of monocarboxylate transporters (\n                    <jats:italic>CG8468<\/jats:italic>\n                    ), a member of the lipocalin protein family (\n                    <jats:italic>CG5399<\/jats:italic>\n                    ), and a zinc finger C2H2 transcription factor (\n                    <jats:italic>CG9932<\/jats:italic>\n                    ). Mechanistically, we demonstrate that\n                    <jats:italic>CG5399<\/jats:italic>\n                    overexpression activates the RTK-Akt-mTOR signaling pathway and that activation of insulin receptor (InR) by\n                    <jats:italic>CG5399<\/jats:italic>\n                    requires cholesterol and clathrin-coated pits at the cell membrane. This study establishes a novel platform for functional genetic studies in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    cells.\n                  <\/jats:p>","DOI":"10.7554\/elife.85542","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T06:15:15Z","timestamp":1681107315000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.85542","source":"Crossref","is-referenced-by-count":15,"title":["Pooled genome-wide CRISPR activation screening for rapamycin resistance genes in Drosophila cells"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2536-0267","authenticated-orcid":true,"given":"Baolong","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Genetics, Blavatnik Institute, Harvard Medical School","place":["Boston, United 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