Format

Send to

Choose Destination
PLoS One. 2009 Aug 14;4(8):e6653. doi: 10.1371/journal.pone.0006653.

Epigenetic engineering of ribosomal RNA genes enhances protein production.

Author information

1
Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. raffaella.santoro@bsse.ethz.ch

Abstract

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 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.

PMID:
19680546
PMCID:
PMC2721416
DOI:
10.1371/journal.pone.0006653
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center