Global approaches to the role of miRNAs in drug-induced changes in gene expression
- 1 Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA
- 2 Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA
- 3 Department of Molecular, Microbial and Structural Biology, University of Connecticut Health Center, Farmington, CT, USA
Neurons modulate gene expression with subcellular precision through excitation-coupled local protein synthesis, a process that is regulated in part through the involvement of microRNAs (miRNAs), a class of small non-coding RNAs. The biosynthesis of miRNAs is reviewed, with special emphasis on miRNA families, the subcellular localization of specific miRNAs in neurons, and their potential roles in the response to drugs of abuse. For over a decade, DNA microarrays have dominated genome-wide gene expression studies, revealing widespread effects of drug exposure on neuronal gene expression. We review a number of recent studies that explore the emerging role of miRNAs in the biochemical and behavioral responses to cocaine. The more powerful next-generation sequencing technology offers certain advantages and is supplanting microarrays for the analysis of complex transcriptomes. Next-generation sequencing is unparalleled in its ability to identify and quantify low-abundance transcripts without prior sequence knowledge, facilitating the accurate detection and quantification of miRNAs expressed in total tissue and miRNAs localized to postsynaptic densities (PSDs). We previously identified cocaine-responsive miRNAs, synaptically enriched and depleted miRNA families, and confirmed cocaine-induced changes in protein expression for several bioinformatically predicted target genes. The miR-8 family was found to be highly enriched and cocaine-regulated at the PSD, where its members may modulate expression of cell adhesion molecules. An integrative approach that combines mRNA, miRNA, and protein expression profiling in combination with focused single gene studies and innovative behavioral paradigms should facilitate the development of more effective therapeutic approaches to treat addiction.
Keywords: cocaine, RNA-Seq, postsynaptic density, cell adhesion, miR-8, microRNAs, synaptic plasticity
Citation: Eipper-Mains JE, Eipper BA and Mains RE (2012) Global approaches to the role of miRNAs in drug-induced changes in gene expression. Front. Gene. 3:109. doi: 10.3389/fgene.2012.00109
Received: 01 March 2012; Accepted: 29 May 2012;
Published online: 13 June 2012.
, Georgia Health Sciences University, USA
Copyright: © 2012 Eipper-Mains, Eipper and Mains. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Richard E. Mains, Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3401, USA. e-mail: firstname.lastname@example.org