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Programmable protein expression using a genetically encoded m6A sensor

delete2024-01-02
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PRE
AI
B
Bahjat Fadi Marayati
M
Matthew G. Thompson
C
Christopher L. Holley
S
Stacy M. Horner
K
Kate D. Meyer *
DOI:10.1038/s41587-023-01978-3delete
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Abstract

Abstract

En 中文
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.
Keywords:
SINGLE-NUCLEOTIDE-RESOLUTION
RNA METHYLATION
MESSENGER-RNA
P53
N-6-METHYLADENOSINE
READERS
WRITERS
GENE

Journal

Nature Biotechnology cover
Nature Biotechnology
IF:
41.7
Papers:
1.2W
Citations:
10.1W

Organization

D
Duke University
Scholars:
6.3W
Papers: 5.7W
Citations: 6.5W
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