YTHDF2 alleviates microglia activation via promoting circHIPK2 degradation

Area of Science:

• Neuroscience
• Molecular Biology
• Immunology

Background:

• Microglial activation is a hallmark of central nervous system inflammation, often involving dysregulated circular RNA (circRNA) expression.
• YTH domain-containing protein 2 (YTHDF2) is an N⁶-methyladenosine (m⁶A) reader crucial for RNA degradation.

Purpose of the Study:

• To investigate the role of YTHDF2 and circHIPK2 in lipopolysaccharide (LPS)-induced microglia activation.
• To explore the potential of targeting YTHDF2 for therapeutic intervention in neuroinflammation.

Main Methods:

• Induced microglia activation using lipopolysaccharide (LPS) in mouse cortex and BV2 cell models.
• Assessed the expression levels of YTHDF2 and circHIPK2.
• Manipulated YTHDF2 and circHIPK2 expression to evaluate their impact on inflammatory markers.

Main Results:

• LPS-induced microglia activation was associated with decreased YTHDF2 and increased circHIPK2 expression.
• YTHDF2 overexpression or circHIPK2 knockdown significantly inhibited the expression of iNOS, IL-1β, and IL-6.
• YTHDF2 was found to promote the degradation of circHIPK2, thereby mitigating microglia activation.

Conclusions:

• YTHDF2 plays a protective role by degrading circHIPK2, thus suppressing microglia activation.
• YTHDF2 overexpression presents a potential therapeutic strategy for managing neuroinflammation.