Extracellular communication via microRNA: lipid particles have a new message

Abstract

In the decade following the discovery that the mammalian genome contained functional microRNA (miRNA) sequences, there has been an explosion in our understanding of how these tiny powerhouse nucleic acids mediate such elegant control over gene function. This has been further exemplified by the recent ENCyclopedia Of DNA Elements (ENCODE) project revelation that over 90% of the human genome is comprised of functional noncoding RNA, which prompted a revisiting of this previously disregarded genetic information (1). miRNAs are a specific class of noncoding RNA (ncRNA), and are defined as small, 20–22 nucleotide RNA molecules that are processed from a much larger primary transcript. Once processed into their mature form, miRNAs generally bind to complimentary sequences in the 3′ untranslated region (UTR) of specific genes but can also bind to other regions of the gene including the 5′ UTR and the coding region (2, 3). Via mRNA destabilization and/or protein translation inhibition, miRNAs mediate silencing of their bound targets. Recently, the importance of miRNAs in the extracellular space has been exemplified by a number of studies showing specific and regulated export of miRNA from the cell, and the uptake and functional consequences in recipient cells. Moreover, circulating miRNAs are emerging as attractive biomarkers in various disease states, including cancer, cardiovascular disease, and diabetes, owing to their ease of detection and inherent molecular stability. In this review, we will discuss the various routes of export of miRNAs into the extracellular space, what the consequences of this may be, and how miRNAs in the circulation may give us hints of the underlying biology of certain disease states.