title: The 3'UTR of HIC mRNA improves the production of recombinant proteins in Chinese hamster ovary cells.
abstract: Positive transcription elongation factor b (P-TEFb) is an important transcriptional regulator which controls 70-80% of RNA polymerase II transcription. It has been reported that the human I-mfa (inhibitor of MyoD family a) domain-containing protein (HIC) interacts with P-TEFb and that expression of HIC cDNA stimulates P-TEFb-dependent transcription. Interestingly, our recent study shows that transcriptional stimulation by HIC is predominately due to the 3' untranslated region (3'UTR) of HIC mRNA rather than its coding region. In this report, we investigate the effects of HIC 3'UTR on recombinant protein expression in mammalian cells. In transient transfections, overexpression of HIC 3'UTR stimulates transgene expression in several mammalian cell lines and significantly increases the production of human erythropoietin and interferon-gamma in Chinese hamster ovary (CHO) cells. This is the first report that demonstrates the improvement of expression of biopharmaceutical proteins by overexpressing a non-coding 3'UTR in CHO cells.
authors.affiliation: Expression Engineering Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore,
authors.forename: Jaron
authors.initials: J
authors.lastname: Liu
authors.forename: Sebastian C Y
authors.initials: SC
authors.lastname: Ku
authors.forename: Jialing
authors.initials: J
authors.lastname: Lee
authors.forename: Tara M
authors.initials: TM
authors.lastname: Young
authors.forename: Tsafi
authors.initials: T
authors.lastname: Pe'ery
authors.forename: Michael B
authors.initials: MB
authors.lastname: Mathews
authors.forename: Sheng-Hao
authors.initials: SH
authors.lastname: Chao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008954:Models, Biological; D018006:Myogenic Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D042925:Positive Transcriptional Elongation Factor B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000235:genetics; D019076:Transgenes
chemical_list: D020413:3' Untranslated Regions; C478034:MDFIC protein, human; D018006:Myogenic Regulatory Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004921:Erythropoietin; D007371:Interferon-gamma; D042925:Positive Transcriptional Elongation Factor B