The 3′UTR of HIC mRNA improves the production of recombinant proteins in Chinese hamster ovary cells

Jaron Liu; Sebastian C.Y. Ku; Jialing Lee; Tara M. Young; Tsafi Pe'ery; Michael B. Mathews; Sheng Hao Chao

doi:10.1016/j.jbiotec.2008.10.008

The 3′UTR of HIC mRNA improves the production of recombinant proteins in Chinese hamster ovary cells

Jaron Liu, Sebastian C.Y. Ku, Jialing Lee, Tara M. Young, Tsafi Pe'ery, Michael B. Mathews, Sheng Hao Chao

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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-γ 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.

Original language	English (US)
Pages (from-to)	152-155
Number of pages	4
Journal	Journal of Biotechnology
Volume	139
Issue number	2
DOIs	https://doi.org/10.1016/j.jbiotec.2008.10.008
State	Published - Jan 15 2009

All Science Journal Classification (ASJC) codes

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology

Keywords

3′UTR
Erythropoietin
Human I-mfa domain-containing protein
Interferon-γ
P-TEFb
RNA polymerase II

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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-γ 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.",

keywords = "3′UTR, Erythropoietin, Human I-mfa domain-containing protein, Interferon-γ, P-TEFb, RNA polymerase II",

author = "Jaron Liu and Ku, {Sebastian C.Y.} and Jialing Lee and Young, {Tara M.} and Tsafi Pe'ery and Mathews, {Michael B.} and Chao, {Sheng Hao}",

note = "Funding Information: We would like to thank Dr. Peter Nissom for critical review of the manuscript. This work is supported by the Agency for Science, Technology and Research, Singapore, the National Institutes of Health (NIH; U.S.) grant AI055331 to TP, and NIH (U.S.) grant AI034552 to MBM.",

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T1 - The 3′UTR of HIC mRNA improves the production of recombinant proteins in Chinese hamster ovary cells

AU - Liu, Jaron

AU - Ku, Sebastian C.Y.

AU - Lee, Jialing

AU - Young, Tara M.

AU - Pe'ery, Tsafi

AU - Mathews, Michael B.

AU - Chao, Sheng Hao

N1 - Funding Information: We would like to thank Dr. Peter Nissom for critical review of the manuscript. This work is supported by the Agency for Science, Technology and Research, Singapore, the National Institutes of Health (NIH; U.S.) grant AI055331 to TP, and NIH (U.S.) grant AI034552 to MBM.

PY - 2009/1/15

Y1 - 2009/1/15

N2 - 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-γ 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.

AB - 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-γ 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.

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