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Programmable protein expression using a genetically encoded m6A sensor
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DOI：10.1038/s41587-023-01978-3.png)
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摘要
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The N-6-methyladenosine (m(6)A) modification is found in thousands of cellular mRNAs and is a critical regulator of gene expression and cellular physiology. m(6)A dysregulation contributes to several human diseases, and the m6A methyltransferase machinery has emerged as a promising therapeutic target. However, current methods for studying m(6)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(6)A sensor (GEMS) technology, which couples a fluorescent signal with cellular mRNA methylation. GEMS detects changes in m(6)A caused by pharmacological inhibition of the m(6)A methyltransferase, giving it potential utility for drug discovery efforts. Additionally, GEMS can be programmed to achieve m(6)A-dependent delivery of custom protein payloads in cells. Thus, GEMS is a versatile platform for m(6)A sensing that provides both a simple readout for m(6)A methylation and a system for m(6)A-coupled protein expression.
Keyword:
SINGLE-NUCLEOTIDE-RESOLUTION
RNA METHYLATION
MESSENGER-RNA
P53
N-6-METHYLADENOSINE
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GENE
期刊
IF:
41.7
论文数:
1.2W
被引数:
10.1W
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