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Characterizing RNA Modifications in Single Neurons Using Mass Spectrometry
Published on: April 21, 2022
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NMDAR mediated dynamic changes in m6A inversely correlates with neuronal translation
Naveen Kumar Chandappa Gowda1,2, Bharti Nawalpuri2, Sarayu Ramakrishna2
1Institute for Stem Cell Science and Regenerative Medicine, Bangalore, 560065, India.
Scientific Reports
|July 5, 2022
Summary
N6 methyladenosine (m6A) RNA modifications regulate neuronal translation and synaptic plasticity. NMDAR stimulation increases m6A, impacting protein synthesis and cellular homeostasis.
Area of Science:
- Neuroscience
- Molecular Biology
- Epigenetics
Background:
- Epitranscriptome modifications, particularly N6 methyladenosine (m6A), are vital for cellular homeostasis and neuronal function.
- The role of m6A in activity-mediated translation and synaptic plasticity remains largely unexplored.
Purpose of the Study:
- To investigate the involvement of m6A modification in response to N-methyl-D-aspartate receptor (NMDAR) stimulation.
- To elucidate the relationship between m6A, translation regulation, and synaptic plasticity.
Main Methods:
- NMDAR stimulation in neuronal cells.
- Measurement of eEF2 phosphorylation and m6A levels.
- Analysis of m6A-marked RNA redistribution.
- Investigation of FTO (FTO alpha-ketoglutarate dependent dioxygenase) levels and function.
Main Results:
- NMDAR stimulation led to increased eEF2 phosphorylation and a significant rise in m6A levels at 5 minutes, correlating with global translation inhibition.
- NMDAR stimulation caused redistribution of m6A-marked RNAs from translating to non-translating ribosomes.
- Increased m6A levels correlated with decreased FTO levels, and FTO inhibition blocked NMDAR-mediated m6A changes.
Conclusions:
- NMDAR-dependent translation regulation involves RNA-based molecular readouts, including m6A modifications.
- These findings provide insights into how changes in protein synthesis are modulated during neuronal activity.
- m6A modification and FTO play a role in activity-dependent translation regulation in neurons.
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