Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain
Article first published online: 12 APR 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 106, Issue 2, pages 650–661, July 2008
How to Cite
Lugli, G., Torvik, V. I., Larson, J. and Smalheiser, N. R. (2008), Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain. Journal of Neurochemistry, 106: 650–661. doi: 10.1111/j.1471-4159.2008.05413.x
- Issue published online: 4 JUL 2008
- Article first published online: 12 APR 2008
- Received January 23, 2008; revised manuscript received March 18, 2008; accepted April 4, 2008.
- fragile X mental retardation protein;
- microRNA precursors;
- post-synaptic density;
- synaptic plasticity
We have characterized the expression of microRNAs and selected microRNA precursors within several synaptic fractions of adult mouse forebrain, including synaptoneurosomes, synaptosomes and isolated post-synaptic densities (PSDs), using methods of microRNA microarray, real time qRT-PCR, Northern blotting and immunopurification using anti-PSD95 antibody. The majority of brain microRNAs (especially microRNAs known to be expressed in pyramidal neurons) are detectably expressed in synaptic fractions, and a subset of microRNAs is significantly enriched in synaptic fractions relative to total forebrain homogenate. MicroRNA precursors are also detectable in synaptic fractions at levels that are comparable to whole tissue. Whereas mature microRNAs are predominantly associated with soluble components of the synaptic fractions, microRNA precursors are predominantly associated with PSDs. For seven microRNAs examined, there was a significant correlation between the relative synaptic enrichment of the precursor and the relative synaptic enrichment of the corresponding mature microRNA. These findings support the proposal that microRNAs are formed, at least in part, via processing of microRNA precursors locally within dendritic spines. Dicer is expressed in PSDs but is enzymatically inactive until conditions that activate calpain cause its liberation; thus, we propose that synaptic stimulation may lead to local processing of microRNA precursors in proximity to the synapse.