caa a22 4500 528785028 20200424032356.0 cr unu---uuuuu 180924s2009 xx s 000 0 eng 10.3929/ethz-b-000015567 doi 10.1371/journal.pone.0006653 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/15567 Santoro Raffaella Epigenetic Engineering of Ribosomal RNA Genes Enhances Protein Production [Elektronische Daten] [Raffaella Santoro, Philipp Lienemann, Martin Fussenegger] PLoS ONE Open access ethresearch Selection of mammalian high-producer cell lines remains a major challenge for the biopharmaceutical manufacturing industry. Ribosomal RNA (rRNA) genes encode the major component of the ribosome but many rRNA gene copies are not transcribed [1]-[5] due to epigenetic silencing by the nucleolar remodelling complex (NoRC) [6], which may limit the cell's full production capacity. Here we show that the knockdown of TIP5, a subunit of NoRC, decreases the number of silent rRNA genes, upregulates rRNA transcription, enhances ribosome synthesis and increases production of recombinant proteins. However, general enhancement of rRNA transcription rate did not stimulate protein synthesis. Our data demonstrates that the number of transcriptionally competent rRNA genes limits efficient ribosome synthesis. Epigenetic engineering of ribosomal RNA genes offers new possibilities for improving biopharmaceutical manufacturing and provides novel insights into the complex regulatory network which governs the translation machinery in normal cellular processes as well as in pathological conditions like cancer. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Lienemann Philipp joint author Fussenegger Martin joint author PLoS ONE Lawrence, KS, USA : Public Library of Science 4 (8), p. e6653 1932-6203 http://hdl.handle.net/20.500.11850/15567 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/15567 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 100 1- Santoro Raffaella ETHRESEARCH 700 1- Lienemann Philipp joint author ETHRESEARCH 700 1- Fussenegger Martin joint author ETHRESEARCH 773 0- PLoS ONE Lawrence, KS, USA : Public Library of Science 4 (8), p. e6653 1932-6203 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access