Synaptic enrichment of microRNAs in adult mouse forebrain is related to structural features of their precursors

Neil R Smalheiser

doi:10.1186/1745-6150-3-44

Abstract

Within mouse forebrain, a subset of microRNAs are significantly enriched in synaptoneurosomes (a synaptic fraction containing pinched-off dendritic spines) and a subset are significantly depleted relative to total forebrain homogenate. Here I show that, as a group, the pre-miR hairpin precursors of synaptically enriched microRNAs exhibit significantly different structural features than those that are non-enriched or depleted. Precursors of synaptically enriched microRNAs tend to have a) shorter uninterrupted double-stranded stem segments, and b) more symmetrical bulges containing a single nucleotide on each side. These structural differences may provide a basis for the differential binding of proteins that mediate dendritic transport of pre-miRs, or that prevent pre-miRs from being prematurely processed into mature miRNAs during the transport process.This article was reviewed by I. King Jordan and Jerzy Jurka.

Highlights

The brain expresses a wide variety of miRNAs, some of which show regional and cell type specificity [1,2,3,4,5,6]. miRNAs are expressed in dendrites where they regulate local protein translation [7,8]
A recent experimental study of adult mouse forebrain reported the expression of miRNAs in synaptoneurosomes (SYN), a synaptic fraction that is enriched in pinched-off dendritic spines [10]
Our previous study in adult mouse forebrain [10] reported that the sets of microRNAs that are enriched vs. depleted in synaptic fractions differ significantly in their tissue expression patterns, evolutionary histories, and overall expression levels

Summary

Introduction

The brain expresses a wide variety of miRNAs, some of which show regional and cell type specificity [1,2,3,4,5,6]. miRNAs are expressed in dendrites where they regulate local protein translation [7,8]. A significant subset of forebrain-expressed miRNAs (34, or about 14%) is enriched (2-fold or greater) in synaptic fractions relative to total forebrain homogenate, as measured by microarray. These SYN-enriched miRNAs are biologically quite distinct from SYN-depleted miRNAs, both in their expression patterns (many SYN-enriched miRNAs are expressed predominantly in pyramidal neurons, whereas SYNdepleted miRNAs tend to have widespread and abundant tissue expression) and in their evolutionary histories (SYN-enriched miRNAs tend to be evolutionarily new, often mammalian-specific or rodent-specific, whereas the SYN-depleted miRNAs tend to be highly conserved across vertebrates and some had homologues in C. elegans). For seven miRNAs examined, there was a significant correlation between the relative synaptic enrichment of the precursor and the relative synaptic enrichment of the corresponding mature (page number not for citation purposes)

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Conclusion