Conditional RNA interference in mammalian cells via RNA transactivation
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Citation
A. Green, Y. Zhou, M. Xie, P. Sheng, J. Li, Y. Li. 2024. "Conditional RNA Interference in Mammalian Cells via RNA Transactivation" Nature Communications, Volume 15, Issue 1, pp.6855-6855. https://doi.org/10.1038/s41467-024-50600-w
Abstract
RNA interference (RNAi) is a powerful tool for sequence-specific knockdown of gene expression in therapeutic and research applications. However, spatiotemporal control of RNAi is required to decrease nonspecific targeting, potential toxicity, and allow targeting of essential genes. Herein we describe a class of de-novo-designed RNA switches that enable sequence-specific regulation of RNAi in mammalian cells. Using cis-repressing RNA elements, we engineered RNA devices that only initiate microRNA biogenesis in response to the binding of a cognate trigger RNA. We demonstrate that this conditional RNAi system, termed Orthogonal RNA Interference induced by Trigger RNA (ORIENTR), provides up to 14-fold increases in miRNA biogenesis upon activation in orthogonal libraries. We show that integration of ORIENTR triggers with deactivated Cas13d enhances dynamic range up to 31-fold. ORIENTRs enable conditional RNAi activation using diverse potential cellular RNA signals, enabling new regulatory possibilities including cell-type-specific RNAi and rewiring of transcriptional networks via RNA profile.
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Attribution 4.0 International
© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.