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Updated: Jan 9, 2026
Use of Alu Element Containing Minigenes to Analyze Circular RNAs
Published on: March 10, 2020
PTBP1-mediated inhibition of circular RNA SCMH1 biogenesis impairs brain recovery after ischemic stroke
Ying Bai1, Bing Han1,2, Yi Zhang1
1Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing 210009, China.
Rationale:
Aberrant circular RNA (circRNA) expression is implicated in various diseases, but the regulatory mechanisms remain poorly understood. Our previous work identified circSCMH1 as a brain repair-associated circRNA, prompting investigation into its biogenesis regulation.
Methods:
We combined computational analysis of RNA-binding protein (RBP) binding sites in flanking intronic regions with transcriptomic sequencing to identify potential circSCMH1 regulators. Molecular biology experiments including RNA immunoprecipitation and functional assays were performed to validate the interaction between candidate RBPs and circSCMH1 precursor sequences.
Results:
Polypyrimidine tract binding protein 1 (PTBP1) was identified as a key regulator binding specifically to the 800-882 segment at the 3' end of circSCMH1's flanking intron. This binding event inhibited back-splicing and reduces circSCMH1 production. Functional studies demonstrated that PTBP1-mediated suppression of circSCMH1 exacerbates post-stroke brain injury.
Conclusions:
Our study reveals a novel molecular mechanism whereby PTBP1 regulates circSCMH1 biogenesis through suppression of back-splicing. These findings advance understanding of circRNA regulatory networks and suggest potential therapeutic targets for stroke recovery.
Insights
Polypyrimidine tract binding protein 1 (PTBP1) suppresses circSCMH1 production by inhibiting back-splicing. This regulation impacts brain repair after stroke, offering potential therapeutic targets for stroke recovery.
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- Aberrant circular RNA (circRNA) expression is linked to various diseases.
- Mechanisms regulating circRNA biogenesis are not fully understood.
- circSCMH1 was previously identified as a circRNA associated with brain repair.
Purpose of the Study:
- Investigate the regulatory mechanisms of circSCMH1 biogenesis.
- Identify RNA-binding proteins (RBPs) that regulate circSCMH1.
- Determine the role of PTBP1 in circSCMH1 production and its impact on stroke.
Main Methods:
- Computational analysis of RBP binding sites in intronic regions.
- Transcriptomic sequencing to identify circRNA regulators.
- RNA immunoprecipitation and functional assays to validate RBP-circRNA interactions.
Main Results:
- Polypyrimidine tract binding protein 1 (PTBP1) binds to circSCMH1 precursor sequences.
- PTBP1 binding inhibits back-splicing, reducing circSCMH1 production.
- PTBP1-mediated suppression of circSCMH1 worsens post-stroke brain injury.
Conclusions:
- PTBP1 is a novel regulator of circSCMH1 biogenesis via suppression of back-splicing.
- This study elucidates a new circRNA regulatory mechanism.
- Findings suggest PTBP1 and circSCMH1 as potential therapeutic targets for stroke recovery.
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