Reilly, Matthew

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Matthew Reilly

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Role of Non-Coding RNAs in the Neuroadaptation to Alcoholism and Fetal Alcohol Exposure

Role of non-coding RNAs in the neuroadaptation to 
alcoholism and fetal alcohol exposure
Matthew Reilly*
Division of Neuroscience and Behavior, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA
*Correspondence: reillymt@mail.nih.gov
genetic vulnerability to alcoholism are warranted, and the burgeon-
ing area of microRNAs appears to be a fruitful area of investigation. 
This is because determining the role of microRNAs in disease will 
offer both mechanistic and potential therapeutic insight.
Gene expression changes after alcohol exposure are well docu-
mented. In particular, a vast network of expression changes are 
found in the brain (and other tissues) following both acute and 
chronic alcohol exposure. These neuroadaptations are thought to 
underlie tolerance and dependence on alcohol as well as mediating 
the toxic effects of alcohol on neurodevelopment. Studies examining 
the effects of alcohol on microRNA expression are just beginning. 
Applying this new information on microRNAs to genome-wide 
studies of gene expression changes after alcohol exposure repre-
sents both a significant challenge and tremendous opportunity for 
unraveling the genetic vulnerability to alcohol dependence. In this 
special issue of Frontiers in Genetics two important areas relevant 
to microRNA biology and alcohol are presented. The first article 
presents recent studies on microRNAs in post-mortem human 
brain samples from alcoholics compared to non-alcoholics. This 
is the first study to profile changes in the expression of microRNAs 
in brain samples from alcoholics. These changes in microRNAs are 
correlated with previously identified gene expression changes to 
provide a glimpse into the possible mechanisms by which alcohol 
neuroadaptation alters the brain. The second article in this spe-
cial issue examines the effects of fetal alcohol exposure on micro-
RNA expression. This exciting area has important implications 
for understanding and treating Fetal Alcohol Syndrome and Fetal 
Alcohol Spectrum Disorders. Collectively, these studies highlight 
the emerging role of microRNAs in neurobiology in general and 
alcohol neuroadaptation specifically. Because microRNAs can fine-
tune gene expression in subtle yet critical ways, harnessing these 
endogenous master regulators holds tremendous promise for the 
identification of novel drug targets and eventually the development 
of new therapeutics to treat alcoholism.
Received: 19 March 2012; accepted: 12 April 2012; published online: 15 June 2012.
Citation: Reilly M (2012) Role of non-coding RNAs in the neuroadaptation to alcoholism 
and fetal alcohol exposure. Front. Gene. 3:70. doi: 10.3389/fgene.2012.00070
This article was submitted to Frontiers in Non-Coding RNA, a specialty of Frontiers in 
Genetics.
Copyright © 2012 Reilly. 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.
The control of gene expression is a fundamental process in all of 
biology. Understanding the mechanisms by which genes are turned 
off and on in a temporally and spatially mediated fashion, repre-
sents an area where major scientific advances are likely to occur 
in the next decade. This is because the control of the timing and 
location of gene expression is arguably one of the most critical 
regulation points in determining cellular identity and function and 
when gene regulation is perturbed disease states can arise. Classic 
gene expression control mechanisms such as cis-acting elements 
in gene promoters and trans-acting factors (transcription factor 
proteins) have been well studied. However, the recent discovery of 
gene expression regulation mediated by RNA molecules that are 
transcribed from DNA but do not code for protein, has set into 
motion a revolution in molecular biology. These novel RNAs are 
classified broadly as non-coding RNAs (ncRNAs) and include both 
small (microRNAs or miRNAs) and large classes (long non-coding 
RNAs or lncRNAs) that function to alter the expression of genes to 
which they bind and modify chromatin states. Yet, there remains 
much to be understood about the biology of ncRNAs and how this 
contributes to susceptibility to disease.
Like all complex traits, alcoholism is influenced by multiple 
genetic and environmental factors. In addition, there is significant 
heterogeneity found with alcoholism making it a daunting task to 
identify the specific genes associated with the disease. Although 
progress has been made in identifying some of the genetic vari-
ants, explaining the entire phenotypic variation associated with 
alcoholism is far from complete. Most of the recent efforts in under-
standing the genetic vulnerability to alcoholism have focused on 
genotype-phenotype associations. For example, in the last several 
years there has been an explosion in Genome-Wide Association 
Studies (GWAS), which seek to correlate common genetic variation 
(represented by Single Nucleotide Polymorphisms or SNPs) with 
a particular trait or disease. Success of GWAS has varied across 
different complex traits, where most studies have found that indi-
vidual SNPs account for a very small proportion of the variance. 
This is true for GWAS studies of alcoholism and alcohol-related 
phenotypes, where genome-wide significance has rarely been 
achieved. There are several prevailing hypotheses that have been 
put forth to explain the small effect sizes observed with GWAS and 
other approaches. These include arguments for the contribution of 
untested rare variants, sample power issues, and “phantom herit-
ability.” It is clear, however, that new perspectives for understanding 
www.frontiersin.org June 2012 | Volume 3 | Article 70 | 1
Editorial
published: 15 June 2012
doi: 10.3389/fgene.2012.00070


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