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Deciphering the miR-29c-3p / TET3 regulatory axis within the SARS-CoV-2-infected midbrain
Abigail Dickerson1, Andreea Cruceanu1, Bishwa R Pokharel1
1Department of Microbiology & Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, 27834, USA.
Virology
|June 8, 2026
Summary
Persistent neurological symptoms in Long COVID may involve miR-29c-3p and Ten-Eleven-Translocation 3 (TET3) signaling. Research suggests a potential regulatory role for this pathway in SARS-CoV-2-induced brain effects.
Area of Science:
- Neuroscience
- Molecular Biology
- Virology
Background:
- Long COVID is frequently linked to ongoing neurological issues.
- MicroRNAs (miRNAs) are implicated in post-viral neurological complications.
- The Ten-Eleven-Translocation 3 (TET3) gene plays a role in neurological function.
Purpose of the Study:
- To investigate the regulatory relationship between miR-29c-3p and TET3 in the context of SARS-CoV-2 infection.
- To explore the potential role of miR-29c-3p/TET3 signaling in Long COVID neurological symptoms.
Main Methods:
- Bioinformatic analysis to predict miRNA binding sites.
- Luciferase reporter assays to validate direct targeting.
- In vivo studies using K18-hACE2 mouse model of SARS-CoV-2 infection.
Main Results:
- Bioinformatics predicted multiple miR-29c-3p binding sites in the TET3 3'-UTR.
- Luciferase assays confirmed miR-29c-3p directly binds to an 8 bp sequence in the TET3 3'-UTR.
- An inverse correlation between miR-29c-3p and TET3 expression was observed in the midbrains of virus-positive mice.
- Decreased miR-29c-3p levels were specific to virus-positive brains, suggesting a potential predisposing factor for neuro-invasion.
Conclusions:
- The miR-29c-3p/TET3 signaling pathway is a potential regulator of SARS-CoV-2-induced neurological symptoms.
- Dysregulation of miR-29c-3p may contribute to viral neuro-invasion and Long COVID neurological complications.
- Further research is warranted to elucidate the precise mechanisms and therapeutic potential.
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