Duration Control of Protein Expression in Vivo by Light-Mediated Reversible Activation of Translation

The photocontrol of protein expression enables the spatiotemporal induction of biological events in living cells or organisms. However, commonly used method such as photocontrollable transcription factor or caged nucleic acids is unsuitable for precise control of the duration of protein expression. Here, I report a photocontrollable cap (PC-cap) that can control the translation of mRNA in a reversible manner via its cis-trans photoisomerization through illumination with 370 and 430 nm light. 2-meta-Methyl-phenylazo cap (mMe-2PA-cap) in the trans form silences translation in zebrafish embryo, whereas treatment with the cis form provided a 7.1 times larger amount of translated protein compared to the trans form. Moreover, translation activated by illumination of the embryo with 370 nm light was rapidly inactivated again by subsequent illumination with 430 nm light. An application of this approach was demonstrated by photoinducing the development of double-headed zebrafish by controlling the expression period of squint protein.