Programmable protein expression using a genetically encoded m<sup>6</sup>A sensor.
basic_science · Level V
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- Record sourced from PubMed, PMID 38168988.
- Also identified by DOI 10.1038/s41587-023-01978-3 and PMC identifier 11217150.
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Abstract
The N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification is found in thousands of cellular mRNAs and is a critical regulator of gene expression and cellular physiology. m<sup>6</sup>A dysregulation contributes to several human diseases, and the m<sup>6</sup>A methyltransferase machinery has emerged as a promising therapeutic target. However, current methods for studying m<sup>6</sup>A require RNA isolation and do not provide a real-time readout of mRNA methylation in living cells. Here we present a genetically encoded m<sup>6</sup>A sensor (GEMS) technology, which couples a fluorescent signal with cellular mRNA methylation. GEMS detects changes in m<sup>6</sup>A caused by pharmacological inhibition of the m<sup>6</sup>A methyltransferase, giving it potential utility for drug discovery efforts. Additionally, GEMS can be programmed to achieve m<sup>6</sup>A-dependent delivery of custom protein payloads in cells. Thus, GEMS is a versatile platform for m<sup>6</sup>A sensing that provides both a simple readout for m<sup>6</sup>A methylation and a system for m<sup>6</sup>A-coupled protein expression.
Medical subject headings
- Humans
- Adenosine
- Adenosine/analogs & derivatives
- Adenosine/genetics
- Adenosine/metabolism
- Methyltransferases
- Methyltransferases/genetics
- Methyltransferases/metabolism
- RNA, Messenger
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Methylation
- Biosensing Techniques