Engineering Iron Responses in Mammalian Cells by Signal-Induced Protein Proximity

Abstract

A new synthetic biology engineering strategy integrating chemical reactivity sensing and small molecule induced protein dimerization has been developed to generate artificial Fe signaling circuitry to control tailored cellular events in mammalian cells. The dual function probe ABA-FE18 (Fe-sensing and protein dimerization) derived from ABA was developed and used to control gene activation, signal transduction, and cytoskeletal remodeling in response to Fe. This technology was utilized to design signal circuitry incorporating "AND" and "OR" biologic gates that enables mammalian cells to translate different combinations of Fe and HO signals into predefined biological outputs.

Inducible and reversible RNA N6-methyladenosine editing

“…To introduce the light control capacity in the ABA-CIP-based m 6 A editing platform, we incorporated the photo-caged ABA that allowed the activation of ABA, and therefore, inducing the RNA m 6 A editing, by light. We have shown that ABA can be caged with sensor units responsive to different stimuli and ABA can only be activated to induce CIP-controlled effects when exposed to the corresponding signals including light 46 – 48 . To create a light-inducible m 6 A editing system, we used 4,5-dimethoxy-2-nitrobenzyl (DMNB)-caged ABA, which can be uncaged by UV light 48 .…”

“…This strategy and platform will expand the existing toolbox for studying the dynamic biological function of RNA modifications in biological or disease processes. By caging ABA with other sensor units other than photo-caging groups 46 , 47 , these RNA epigenetic editing events can be coupled to various cellular signals, which can lead to new synthetic biology strategies in engineering mammalian cells for research or therapeutic purposes.…”

Chemical and Light Inducible Epigenome Editing

“…Several light-inducible methods based on CIP have been reported using CIP inducers caged with different photosensitive groups. These caged CIP inducers (including ABA, rapamycin, gibberellic acid, and other synthetic dimerizers) [77,[97][98][99][100][101][102][103][104][105][106][107][108] were inactive for dimerization in the caged form but can be uncaged to regenerate active inducer upon light irradiation. This photo-controlled version of CIP should be readily adaptable for light inducible epigenome editing.…”

ICBS 2017 in Shanghai—Illuminating Life with Chemical Innovation

“…This technology is based on the chemically induced proximity methods, utilizing artificially applied chemical inducers to control the proximity between two chosen cellular proteins and, in turn, control the downstream events resulting from protein association. 75,76…”