{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:11:01Z","timestamp":1768486261000,"version":"3.49.0"},"posted":{"date-parts":[[2019,10,16]]},"group-title":"Molecular Biology","reference-count":58,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2019,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Dis3L2 is a highly conserved 3\u2019-5\u2019 exoribonuclease which is mutated in the human overgrowth disorders Perlman syndrome and Wilms\u2019 tumour. Here, we have generated a new\n                  <jats:italic>dis3L<\/jats:italic>\n                  2 null mutant and a UAS-nuclease-dead line in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  to demonstrate that the catalytic activity of Dis3L2 is required to control proliferation in imaginal discs. Using RNA-seq on\n                  <jats:italic>dis3L2<\/jats:italic>\n                  mutant wing discs, we show that the imaginal disc growth factor Idgf2 is responsible for driving the wing overgrowth observed in\n                  <jats:italic>dis3L2<\/jats:italic>\n                  null mutants. IDGFs are conserved proteins homologous to human chitinase-like proteins such as CHI3L1\/YKL-40 which are implicated in tissue regeneration as well as cancers including colon cancer and non-small cell lung cancer. We also show that loss of DIS3L2 in human HEK-293T cells results in cell proliferation, illustrating the conservation of this important cell proliferation pathway. Using these human cells we show that loss of DIS3L2 results in an increase in the activity of the PI3-Kinase\/AKT signalling pathway, which we subsequently show to also have a role in driving the proliferation phenotype in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  . Our work therefore provides the first mechanistic explanation for DIS3L2-induced overgrowth in humans and flies and identifies an ancient proliferation pathway controlled by Dis3L2 to regulate cell proliferation and tissue growth.\n                <\/jats:p>","DOI":"10.1101\/806109","type":"posted-content","created":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T19:19:05Z","timestamp":1571253545000},"source":"Crossref","is-referenced-by-count":1,"title":["Dis3L2 regulates cellular proliferation through a PI3-Kinase dependent signalling pathway"],"prefix":"10.64898","author":[{"given":"Benjamin P.","family":"Towler","sequence":"first","affiliation":[]},{"given":"Amy L.","family":"Pashler","sequence":"additional","affiliation":[]},{"given":"Hope J.","family":"Haime","sequence":"additional","affiliation":[]},{"given":"Katarzyna M.","family":"Przybyl","sequence":"additional","affiliation":[]},{"given":"Sandra C.","family":"Viegas","sequence":"additional","affiliation":[]},{"given":"Rute G.","family":"Matos","sequence":"additional","affiliation":[]},{"given":"Simon J.","family":"Morley","sequence":"additional","affiliation":[]},{"given":"Cecilia M.","family":"Arraiano","sequence":"additional","affiliation":[]},{"given":"Sarah F.","family":"Newbury","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2019101804554285000_806109v1.1","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1080\/15476286.2016.1232238","article-title":"A novel role for the 3\u2032-5\u2032 exoribonuclease Dis3L2 in controlling cell proliferation and tissue growth","volume":"13","year":"2016","journal-title":"RNA Biol"},{"key":"2019101804554285000_806109v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1071"},{"key":"2019101804554285000_806109v1.3","first-page":"106","article-title":"Perlman syndrome: overgrowth, Wilms tumor predisposition and DIS3L2","volume":"163c","year":"2013","journal-title":"American journal of medical genetics. 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