Optogenetic control of RNA function and metabolism usingengineered light-switchable RNA-binding proteins

RNA-binding proteins (RBPs) play an essential role in regulating the function of RNAs in a cellular context, but our ability to control RBP activity in time and space is limited. Here, we describe the engineering of LicV, a photoswitchable RBP that binds to a specific RNA sequence in response to blu...

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Bibliographic Details
Published in:Nature biotechnology 2022-05, Vol.40 (5), p.779-786
Main Authors: Liu, Renmei, Yang, Jing, Yao, Jing, Zhao, Zhou, He, Wei, Su, Ni, Zhang, Zeyi, Zhang, Chenxia, Zhang, Zhuo, Cai, Haibo, Zhu, Linyong, Zhao, Yuzheng, Quan, Shu, Chen, Xianjun, Yang, Yi
Format: Article
Language:eng ; jpn
Subjects:
Binding
Cell culture
CRISPR
Effectors
Gene regulation
Irradiation
Light irradiation
Localization
Nucleotide sequence
Proteins
Radiation
Ribonucleic acid
RNA
RNA-binding protein
Splicing
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Summary:RNA-binding proteins (RBPs) play an essential role in regulating the function of RNAs in a cellular context, but our ability to control RBP activity in time and space is limited. Here, we describe the engineering of LicV, a photoswitchable RBP that binds to a specific RNA sequence in response to blue light irradiation. When fused to various RNA effectors, LicV allows for optogenetic control of RNA localization, splicing, translation and stability in cell culture. Furthermore, LicV-assisted CRISPR–Cas systems allow for efficient and tunable photoswitchable regulation of transcription and genomic locus labeling. These data demonstrate that the photoswitchable RBP LicV can serve as a programmable scaffold for the spatiotemporal control of synthetic RNA effectors.Photoswitchable RNA-binding proteins enable the spatiotemporal control of RNA function.
ISSN:1087-0156
1546-1696
DOI:10.1038/s41587-021-01112-1