2011 Fiscal Year Final Research Report
Role of mammalian transcription elongation factor Elongin A in mouse neural development
| Project/Area Number |
21590233
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Kochi University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2011
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| Keywords | 遺伝 / 受精 / 発生 / 分化 |
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| Research Abstract |
Elongin A is an RNA polymerase II(Pol II) transcription elongation factor that increases the rate of Pol II transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as the substrate recognition subunit of a cullin 5(Cul5)-containing cullin-RING ligase(CRL) that can target stalled Pol II for ubiquitination and degradation by the proteasome. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient(Elongin A^<-/->) mouse embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A^<-/-> embryonic stem cells show a markedly decreased capacity to differentiate into neurons. We identify Elongin A mutations that selectively interfere with its the ability to stimulate pol II elongation or to assemble with Cul5 into a functional ubiquitin ligase, and we show that the elongation stimulatory, but not Rpb1 ubiquitylation, activity of Elongin A is required to rescue neuronal differentiation and support retinoic acid-induced up-regulation of a subset of neurogenesis-related and other genes in Elongin A^<-/-> ES cells. These findings identify an important role for Elongin A and its transcription elongation activity in timely expression of genes critical for neurogenesis
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Research Products
(4 results)
