Programmable protein expression using a genetically encoded m 6 A sensor.
Bahjat F MarayatiMatthew G ThompsonChristopher L HolleyStacy M HornerKate D MeyerPublished in: Nature biotechnology (2024)
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 m 6 A 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.
Keyphrases
- living cells
- drug discovery
- dna methylation
- gene expression
- fluorescent probe
- genome wide
- induced apoptosis
- endothelial cells
- single molecule
- binding protein
- cell cycle arrest
- high throughput
- pluripotent stem cells
- induced pluripotent stem cells
- quality improvement
- human health
- risk assessment
- amino acid
- cell death
- climate change
- pi k akt
- genome wide analysis