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青鳉鱼的Tol1转座元件可在人类和小鼠细胞中移动。

The Tol1 transposable element of the medaka fish moves in human and mouse cells.

作者信息

Koga Akihiko, Shimada Atsuko, Kuroki Toshiya, Hori Hiroshi, Kusumi Junko, Kyono-Hamaguchi Yoriko, Hamaguchi Satoshi

机构信息

Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, 464-8602, Japan.

Department of Biological Sciences, Graduate School of Sciences, University of Tokyo, Tokyo, 113-0033, Japan.

出版信息

J Hum Genet. 2007;52(7):628-635. doi: 10.1007/s10038-007-0161-2. Epub 2007 Jun 7.

Abstract

DNA-based transposable elements can be used as tools for gene engineering and gene therapy. A great advantage over RNA-mediated elements and retroviruses is the simplicity and safety of usage. The Tol1 element of the medaka fish Oryzias latipes has structural features of DNA-based elements. Although its excision has already been demonstrated, de novo insertion has not been observed, and a transposase has not been hitherto identified. We first cloned, through in silico search alignments and genomic library screenings, a 4.4-kb Tol1 copy carrying open reading frames and then identified, by mRNA analysis, a 2.9-kb transcript coding for 851 amino acids. The protein product of this transcript catalyzed transposition of a nonautonomous Tol1 copy in human and mouse culture cells. This identification of a fully functional Tol1 transposase could lead to the development of new tools for basic and translational molecular biology applications in mammals.

摘要

基于DNA的转座元件可作为基因工程和基因治疗的工具。与RNA介导元件和逆转录病毒相比,其一大优势在于使用的简便性和安全性。青鳉鱼(Oryzias latipes)的Tol1元件具有基于DNA的元件的结构特征。尽管其切除已得到证实,但尚未观察到从头插入现象,且迄今为止尚未鉴定出转座酶。我们首先通过电子搜索比对和基因组文库筛选,克隆出一个携带开放阅读框的4.4 kb Tol1拷贝,然后通过mRNA分析鉴定出一个编码851个氨基酸的2.9 kb转录本。该转录本的蛋白质产物催化了非自主Tol1拷贝在人和小鼠培养细胞中的转座。这种功能性完全的Tol1转座酶的鉴定可能会推动哺乳动物基础和转化分子生物学应用新工具的开发。

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