Manipulating eukaryotic messenger RNA (mRNA) offers a convenient and efficient approach for regulating gene expression. Here, we demonstrate the activation of cellular protein translation upon photocleavage of small molecule cages tethered to the 5′ untranslated region (5′ UTR) of an mRNA using visible light. These photo-cleavable cages can be conjugated to <i>in vitro</i> transcribed mRNA through enzymatic RNA transglycosylation and severely reduce the level of protein translation when strategically placed in the 5′ UTR. Using this method, we demonstrate the successful spatiotemporal photo-regulation of gene expression with single cell precision. Additionally, our method can be applied to therapeutically relevant chemically modified mRNA (mod-mRNA) transcripts<i>.</i> To the best of our knowledge, this is the first example of photo-regulation of translation through covalent site-specific post-transcriptional modification of mRNA. We believe that this modular and efficient approach has the potential to impact future work in genetic research and therapeutic discovery.

Spatiotemporal photo-regulation of translation by enzymatic covalent mRNA labeling

255th National Meeting (2018)

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