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Identification of Natural Antisense Transcripts in Mouse Brain and Their Association With Autism Spectrum Disorder
Baran Koç1,2,3, Geoffrey Fucile4, Roland Schmucki2,5
1Faculty of Science, University of Basel, Basel, Switzerland.
Frontiers in Molecular Neuroscience
|March 15, 2021
Summary
Natural antisense transcripts (NATs) regulate over 70% of autism spectrum disorder (ASD)-related genes in the mouse brain. This study reveals widespread NAT involvement in ASD gene expression, offering new therapeutic targets.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Autism spectrum disorder (ASD) is a neurodevelopmental condition with a complex genetic basis.
- Natural antisense transcripts (NATs) are RNA molecules transcribed from the opposite strand of protein-coding genes and can regulate gene expression.
- A subset of ASD-related genes express NATs, but their comprehensive role in ASD pathogenesis remains underexplored.
Purpose of the Study:
- To investigate the transcriptional relationship between ASD-related genes and their NATs in the mouse brain.
- To identify and characterize novel NATs associated with ASD-related genes.
- To explore the developmental and regional expression patterns of these NATs.
Main Methods:
- Strand-specific, deep RNA sequencing of mouse medial prefrontal cortex and striatum at postnatal days P7, P14, and P56.
- De novo transcriptome assembly to identify novel long non-coding RNAs (lncRNAs) and antisense transcripts.
- BLAST analysis to compare mouse transcripts with the human genome and quantitative PCR (qPCR) for validation.
Main Results:
- Over 70% (72/100) of examined ASD-related genes exhibited expression of one or more NATs.
- A comprehensive antisense transcriptome was assembled, including 32,861 de novo antisense transcripts mapped to 12,182 genes.
- Expression levels of NATs were generally positively correlated with their cognate sense-strand ASD genes, with some brain region-specific patterns observed.
Conclusions:
- NATs are extensively involved in the regulation of ASD-related genes in the mouse brain, suggesting a broader role than previously recognized.
- The identified antisense transcriptome provides a valuable resource for understanding NAT-mediated gene regulation in neurodevelopment.
- These findings support NAT-based regulatory mechanisms in ASD and offer potential targets for novel therapeutic strategies.
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