Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation

Takashi Yasukawa; Shachi Bhatt; Tamotsu Takeuchi; Junya Kawauchi; Hidehisa Takahashi; Aya Tsutsui; Takuya Muraoka; Makoto Inoue; Masayuki Tsuda; Shigetaka Kitajima; Ronald C. Conaway; Joan W. Conaway; Paul A. Trainor; Teijiro Aso

doi:10.1016/j.celrep.2012.09.031

Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation

Takashi Yasukawa, Shachi Bhatt, Tamotsu Takeuchi, Junya Kawauchi, Hidehisa Takahashi, Aya Tsutsui, Takuya Muraoka, Makoto Inoue, Masayuki Tsuda, Shigetaka Kitajima, Ronald C. Conaway, Joan W. Conaway, Paul A. Trainor, Teijiro Aso

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

16 Scopus citations

Abstract

Elongin A increases the rate of RNA polymerase II (pol II) transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome-dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A^-/-) embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A^-/- embryonic stem cells (ESCs) show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the aforementioned activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced upregulation of a subset of neurogenesis-related genes in Elongin A^-/- ESCs.

Original language	English (US)
Pages (from-to)	1129-1136
Number of pages	8
Journal	Cell Reports
Volume	2
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2012.09.031
State	Published - Nov 29 2012
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2012.09.031

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Yasukawa, T., Bhatt, S., Takeuchi, T., Kawauchi, J., Takahashi, H., Tsutsui, A., Muraoka, T., Inoue, M., Tsuda, M., Kitajima, S., Conaway, R. C., Conaway, J. W., Trainor, P. A., & Aso, T. (2012). Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation. Cell Reports, 2(5), 1129-1136. https://doi.org/10.1016/j.celrep.2012.09.031

Yasukawa, T, Bhatt, S, Takeuchi, T, Kawauchi, J, Takahashi, H, Tsutsui, A, Muraoka, T, Inoue, M, Tsuda, M, Kitajima, S, Conaway, RC, Conaway, JW, Trainor, PA & Aso, T 2012, 'Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation', Cell Reports, vol. 2, no. 5, pp. 1129-1136. https://doi.org/10.1016/j.celrep.2012.09.031

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title = "Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation",

abstract = "Elongin A increases the rate of RNA polymerase II (pol II) transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome-dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A-/-) embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A-/- embryonic stem cells (ESCs) show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the aforementioned activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced upregulation of a subset of neurogenesis-related genes in Elongin A-/- ESCs.",

author = "Takashi Yasukawa and Shachi Bhatt and Tamotsu Takeuchi and Junya Kawauchi and Hidehisa Takahashi and Aya Tsutsui and Takuya Muraoka and Makoto Inoue and Masayuki Tsuda and Shigetaka Kitajima and Conaway, {Ronald C.} and Conaway, {Joan W.} and Trainor, {Paul A.} and Teijiro Aso",

note = "Funding Information: We thank Katsuhisa Yamazaki for anti-Elongin A antibody, Yusaku Nakabeppu for CCE ESCs, and Hitoshi Niwa for pCAG-IPG plasmid. We are grateful to Robb Krumlauf for advice and helpful discussions. This work was supported by KAKENHI (21590233 and 24590279 to T.Y.; 17390082, 21590311, and 24590357 to T.A.), the Life Science Foundation of Japan (to T.Y. and T.A.), the Kochi Shin-kin/Anshin-tomo-no-kai Prize (to T.Y.), the Head of Kochi Medical School Hospital{\textquoteright}s Discretionary Grant (to T.Y. and T.A.), the Joint Usage/Research Program of Tokyo Medical and Dental University (to T.A.), NIH Grant GM41628 (to R.C.C. and J.W.C.), and by funds from the Stowers Institute for Medical Research (to R.C.C., J.W.C., and P.A.T.). ",

year = "2012",

month = nov,

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doi = "10.1016/j.celrep.2012.09.031",

language = "English (US)",

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T1 - Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation

AU - Yasukawa, Takashi

AU - Bhatt, Shachi

AU - Takeuchi, Tamotsu

AU - Kawauchi, Junya

AU - Takahashi, Hidehisa

AU - Tsutsui, Aya

AU - Muraoka, Takuya

AU - Inoue, Makoto

AU - Tsuda, Masayuki

AU - Kitajima, Shigetaka

AU - Conaway, Ronald C.

AU - Conaway, Joan W.

AU - Trainor, Paul A.

AU - Aso, Teijiro

N1 - Funding Information: We thank Katsuhisa Yamazaki for anti-Elongin A antibody, Yusaku Nakabeppu for CCE ESCs, and Hitoshi Niwa for pCAG-IPG plasmid. We are grateful to Robb Krumlauf for advice and helpful discussions. This work was supported by KAKENHI (21590233 and 24590279 to T.Y.; 17390082, 21590311, and 24590357 to T.A.), the Life Science Foundation of Japan (to T.Y. and T.A.), the Kochi Shin-kin/Anshin-tomo-no-kai Prize (to T.Y.), the Head of Kochi Medical School Hospital’s Discretionary Grant (to T.Y. and T.A.), the Joint Usage/Research Program of Tokyo Medical and Dental University (to T.A.), NIH Grant GM41628 (to R.C.C. and J.W.C.), and by funds from the Stowers Institute for Medical Research (to R.C.C., J.W.C., and P.A.T.).

PY - 2012/11/29

Y1 - 2012/11/29

N2 - Elongin A increases the rate of RNA polymerase II (pol II) transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome-dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A-/-) embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A-/- embryonic stem cells (ESCs) show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the aforementioned activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced upregulation of a subset of neurogenesis-related genes in Elongin A-/- ESCs.

AB - Elongin A increases the rate of RNA polymerase II (pol II) transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome-dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A-/-) embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A-/- embryonic stem cells (ESCs) show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the aforementioned activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced upregulation of a subset of neurogenesis-related genes in Elongin A-/- ESCs.

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JO - Cell Reports

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ER -

Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation

Abstract

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