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miR-92a Suppresses Mushroom Body-Dependent Memory Consolidation in Drosophila
Tugba Guven-Ozkan1, Germain U Busto1, Jae-Yoon Jung2
1Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458.
Abstract:
MicroRNAs (miRNAs) fine tune gene expression to regulate many aspects of nervous system physiology. Here, we show that miR-92a suppresses memory consolidation that occurs in the αβ and γ mushroom body neurons (MBns) of Drosophila, making miR-92a a memory suppressor miRNA. Bioinformatics analyses suggested that mRNAs encoding kinesin heavy chain 73 (KHC73), a protein that belongs to Kinesin-3 family of anterograde motor proteins, may be a functional target of miR-92a. Behavioral studies that employed expression of khc73 with and without its 3' untranslated region (UTR) containing miR-92a target sites, luciferase assays in HEK cells with reporters containing wild-type and mutant target sequences in the khc73 3'UTR, and immunohistochemistry experiments involving KHC73 expression with and without the wild-type khc73 3'UTR, all point to the conclusion that khc73 is a major target of miR-92a in its functional role as a miRNA memory suppressor gene.
Insights
MicroRNA-92a (miR-92a) acts as a memory suppressor in Drosophila by inhibiting memory consolidation in mushroom body neurons. It targets kinesin heavy chain 73 (KHC73), a key motor protein, to regulate this process.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are crucial regulators of gene expression in the nervous system.
- Dysregulation of miRNAs can impact neurological functions, including memory.
- Mushroom body neurons (MBns) in Drosophila are vital for learning and memory.
Purpose of the Study:
- To investigate the role of miR-92a in memory consolidation in Drosophila.
- To identify the molecular targets of miR-92a involved in memory regulation.
- To elucidate the mechanism by which miR-92a influences memory suppressor functions.
Main Methods:
- Bioinformatic analysis to predict miRNA targets.
- Behavioral assays in Drosophila to assess memory consolidation.
- Luciferase reporter assays in HEK cells to validate miRNA-target interactions.
- Immunohistochemistry to examine protein expression levels.
Main Results:
- miR-92a was identified as a suppressor of memory consolidation in Drosophila MBns.
- Kinesin heavy chain 73 (KHC73) was predicted and validated as a direct target of miR-92a.
- Experimental evidence confirmed that KHC73 is a major target of miR-92a in the context of memory suppression.
Conclusions:
- miR-92a plays a significant role in suppressing memory consolidation in Drosophila.
- The KHC73 gene is a key molecular target through which miR-92a exerts its memory suppressor function.
- Understanding this miRNA-gene interaction provides insights into the molecular mechanisms of memory regulation.
