In vivo role of transcriptional elongation/ubiquitin ligase factor Elongin

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590357
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kochi University
• Principal Investigator: ASO Teijiro 高知大学, 教育研究部医療学系, 教授 (20291289)
• Co-Investigator(Renkei-kenkyūsha): KITAJIMA Shigetaka 東京医科歯科大学, 難治疾患研究所, 教授 (30186241)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Elongin / 転写伸長 / ユビキチンリガーゼ / RNAポリメラーゼII / 神経分化 / 遺伝子発現 / 神経堤

Outline of Final Research Achievements

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 above 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 up-regulation of a subset of neurogenesis-related genes in Elongin A-/- ESCs.

Free Research Field

医歯薬学