Abstract

microRNAs are short, noncoding RNAs that can regulate hundreds of targets and thus shape the expression landscape of a cell. Similar to mRNA, they often exhibit cell type enriched expression and serve to reinforce cellular identity. In tissue with high cellular complexity, such as the central nervous system (CNS), it is difficult to attribute microRNA changes to a particular cell type. To facilitate interpretation of microRNA studies in these tissues, we used previously generated data to develop a publicly accessible and user-friendly database to enable exploration of cell type enriched microRNA expression. We provide illustrations of how this database can be utilized as a reference as well as for hypothesis generation. First, we suggest a putative role for miR-21 in the microglial spinal injury response. Second, we highlight data indicating that differential microRNA expression, specifically miR-326, may in part explain regional differences in inflammatory cells. Finally, we show that miR-383 expression is enriched in cortical glutamatergic neurons, suggesting a unique role in these cells. These examples illustrate the database’s utility in guiding research towards unstudied regulators in the CNS. This novel resource will aid future research into microRNA-based regulatory mechanisms responsible for cellular phenotypes within the CNS.

Highlights

  • MicroRNAs are short, regulatory RNA molecules that become functionally active after being incorporated into the RNA-induced silencing complex (RISC), containing Argonaute-21,2

  • The field remains hindered by a lack of a thorough cell type specific analysis of miRNA expression across the central nervous system (CNS)

  • We describe the creation of a website to provide a platform for comparing miRNA expression for various cell types within nervous system tissue using data generated in Hoye et al, 201714 and He et al, 20129

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Summary

Introduction

MicroRNAs (miRNAs) are short, regulatory RNA molecules that become functionally active after being incorporated into the RNA-induced silencing complex (RISC), containing Argonaute-21,2. The “Claret” colored frame indicates that miR-21a-5p is broadly conserved among most vertebrate, usually including zebrafish To solve this second problem, we pooled data across studies utilizing this Cre-dependent miRNA affinity purification technique[9] to identify cell type specific miRNAs across major cell types within the mouse CNS. In addition to the He study, we previously leveraged this affinity purification technique to identify miRNAs known to be important for particular cell types, such as the motor neuron-enriched miR-21810–12. This discovery enabled further study of how aberrant miR-218 expression in cell types that do not physiologically express miR-218, such as astrocytes, mediates their dysfunction in a disease like amyotrophic lateral sclerosis[13]. Our resource will assist future hypothesis generation and experimental analyses by informing on specific miRNA-mediated regulatory mechanisms in particular nervous system cell types

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