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m6A Reader Igf2bp1 Regulates the Inflammatory Responses of Microglia by Stabilizing Gbp11 and Cp mRNAs
Lu Ding1, Huiran Wu1, Yi Wang2
1Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
Abstract:
Microglia are brain resident cells that function as brain phagocytic macrophages. The inflammatory responses of microglia induced by pathologic insults are key regulators in the progression of various neurological disorders. Currently, little is known about how these responses are regulated intrinsically. Here, it is observed that LPS-activated microglia exhibit distinct N6-methyladenosine (m6A) methylation patterns that are positively correlated with the expression patterns of corresponding mRNAs. High-throughput analyses and molecular studies both identified Igf2bp1 as the most significantly regulated m6A modifiers in activated microglia. Perturbation of function approaches further indicated Igf2bp1 as a key mediator for LPS-induced m6A modification and microglial activation presumably via enhancing the m6A methylation and stability of Gbp11 and Cp mRNAs. Thus, our study provides a possible mechanism for the m6A methylation-mediated microglia regulation and identifies Igf2bp1 as a potential target for modulating the inflammatory responses of microglia.
Insights
Researchers discovered that N6-methyladenosine (m6A) methylation patterns change in microglia during inflammation. The protein Igf2bp1 was identified as a key regulator of these m6A patterns and microglial activation.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia are the brain's resident phagocytic macrophages.
- Microglial inflammatory responses are crucial in neurological disorders.
- Intrinsic regulation of microglial inflammatory responses remains poorly understood.
Purpose of the Study:
- To investigate the role of N6-methyladenosine (m6A) methylation in regulating microglial inflammatory responses.
- To identify key molecular players involved in m6A-mediated microglial activation.
Main Methods:
- Analysis of m6A methylation patterns in LPS-activated microglia.
- High-throughput sequencing and molecular studies to identify m6A modifiers.
- Functional perturbation studies to assess the role of Igf2bp1.
Main Results:
- LPS-activated microglia show distinct m6A methylation patterns correlated with mRNA expression.
- Igf2bp1 was identified as a significantly regulated m6A modifier in activated microglia.
- Igf2bp1 enhances m6A methylation and stability of Gbp11 and Cp mRNAs, mediating microglial activation.
Conclusions:
- m6A methylation plays a role in regulating microglial inflammatory responses.
- Igf2bp1 is a key mediator of LPS-induced m6A modification and microglial activation.
- Igf2bp1 represents a potential therapeutic target for modulating microglial inflammation.
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