Light-controllable RNA-protein devices for translational regulation of synthetic mRNAs in mammalian cells

被引：16

作者：

Nakanishi, Hideyuki ^{[1
,2
]}

Yoshii, Tatsuyuki ^{[3
,4
]}

Kawasaki, Shunsuke ^{[1
]}

Hayashi, Karin ^{[1
]}

Tsutsui, Keita ^{[3
]}

Oki, Choji ^{[5
]}

Tsukiji, Shinya ^{[3
,5
]}

Saito, Hirohide ^{[1
]}

机构：

[1] Kyoto Univ, Ctr iPS Cell Res & Applicat, Dept Life Sci Frontiers, Sakyo Ku, 53 Kawahara Cho, Kyoto 6068507, Japan

[2] Tokyo Med & Dent Univ TMDU, Inst Biomat & Bioengn, Dept Biofunct Res, Chiyoda Ku, 2-3-10 Kanda Surugadai, Tokyo 1010062, Japan

[3] Nagoya Inst Technol, Dept Life Sci & Appl Chem, Showa Ku, Gokiso Cho, Nagoya, Aichi 4668555, Japan

[4] Japan Sci & Technol Agcy JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 3320012, Japan

[5] Nagoya Inst Technol, Dept Nanopharmaceut Sci, Showa Ku, Gokiso Cho, Nagoya, Aichi 4668555, Japan

来源：

CELL CHEMICAL BIOLOGY | 2021年 / 28卷 / 05期

基金：

日本学术振兴会;

关键词：

OPTOGENETIC CONTROL; GENE CIRCUITS; STABILITY; IDENTIFICATION; PSEUDOURIDINE; DIMERIZATION; ACTIVATION; EXPRESSION;

D O I：

10.1016/j.chembiol.2021.01.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The photo-regulation of transgene expression is one effective approach in mammalian synthetic biology due to its high spatial and temporal resolution. While DNAs are mainly used as vectors, modified RNAs (modRNAs) are also useful for medical applications of synthetic biology, because they can avoid insertional mutagenesis and immunogenicity. However, the optogenetic control of modRNA-delivered transgenes is much more difficult than that of DNA-delivered transgenes. Here, we develop two types of photo-controllable translational activation systems that are compatible with modRNAs. One is composed of a heterodimerization domain-fused split translational activator protein and a photocaged heterodimerizer. The other is composed of a destabilizing domain-fused translational activator protein and a photocaged stabilizer. The destabilized type can be used for not only translational activation but also translational repression of the modRNAs. These photo-controllable translation systems will expand the application of mammalian synthetic biology research.

引用

页码：662 / +

页数：18