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ToxSci Advance Access published online on February 16, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn033
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

miRNAs: effectors of environmental influences on gene expression and disease

Alice Hudder and Raymond F. Novak

Institute of Environmental Health Sciences, Wayne State University, 2727 Second Avenue, Room 4000, Detroit, MI 48201-2654

Director, Institute of Environmental Health Sciences - www.iehs.wayne.edu, Director, EHS Center for Molecular and Cellular Toxicology, with Human Applications - www.ehscenter.org, 2727 Second Avenue, Room 4000, Detroit, MI 48201-2654, Tel.: (313) 577-0100, Fax: (313) 577-0082, Email: r.novak{at}wayne.edu

Received January 16, 2008; revision received February 8, 2008; accepted February 10, 2008


  Abstract

Discovered less than a decade ago, microRNAs (miRNAs) have emerged as important regulators of gene expression in mammals. They consist of short nucleic acids, on average ~22 nucleotides in length. The miRNAs exert their effect by binding directly to target mRNAs and inhibiting mRNA stability and translation. Each miRNA can bind to multiple targets and many miRNAs can bind to the same target mRNA, allowing for a complex pattern of regulation of gene expression. Once bound to their targets, miRNAs can suppress translation of the mRNA by either sequestration or degradation of the message. Thus miRNAs function as powerful and sensitive post-transcriptional regulators of gene expression. This review will summarize what is known about miRNA biogenesis, expression, regulation, function, mode of action, and role in disease processes with an emphasis on miRNAs in mammals. We discuss some of the methodology employed in miRNA research and the potential of miRNAs as therapeutic targets. The role of miRNAs in signal transduction and cellular stress is reviewed. Lastly, we identify new exciting avenues of research on the role of miRNAs in toxicogenomics and the possibility of epigenetic effects on gene expression.

Key Words: microRNAs; translational control; signaling; polysomes; cytochrome P450; toxicants.

Alice.Hudder{at}wayne.edu, r.novak{at}wayne.edu


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