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NMDAR mediated dynamic changes in m6A inversely correlates with neuronal translation

Gowda, NKC and Nawalpuri, B and Ramakrishna, S and Jhaveri, V and Muddashetty, RS (2022) NMDAR mediated dynamic changes in m6A inversely correlates with neuronal translation. In: Scientific Reports, 12 (1).

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Official URL: https://doi.org/10.1038/s41598-022-14798-3


Epitranscriptome modifications are crucial in translation regulation and essential for maintaining cellular homeostasis. N6 methyladenosine (m6A) is one of the most abundant and well-conserved epitranscriptome modifications, which is known to play a pivotal role in diverse aspects of neuronal functions. However, the role of m6A modifications with respect to activity-mediated translation regulation and synaptic plasticity has not been studied. Here, we investigated the role of m6A modification in response to NMDAR stimulation. We have consistently observed that 5Â min NMDAR stimulation causes an increase in eEF2 phosphorylation. Correspondingly, NMDAR stimulation caused a significant increase in the m6A signal at 5Â min time point, correlating with the global translation inhibition. The NMDAR induced increase in the m6A signal is accompanied by the redistribution of the m6A marked RNAs from translating to the non-translating pool of ribosomes. The increased m6A levels are well correlated with the reduced FTO levels observed on NMDAR stimulation. Additionally, we show that inhibition of FTO prevents NMDAR mediated changes in m6A levels. Overall, our results establish RNA-based molecular readout which corelates with the NMDAR-dependent translation regulation which helps in understanding changes in protein synthesis.

Item Type: Journal Article
Publication: Scientific Reports
Publisher: Nature Research
Additional Information: The copyright for this article belongs to the Authors.
Department/Centre: Autonomous Societies / Centres > Centre for Brain Research
Date Deposited: 20 Jul 2022 11:03
Last Modified: 20 Jul 2022 11:03
URI: https://eprints.iisc.ac.in/id/eprint/74932

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