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MicroRNA Profiling by Array Analysis Reveals Critical BioMarkers

he miRNAs are homologous between species, suggesting that miRNAs represent an evolutionally conserved and critical regulatory pathway [11].

The best understood miRNA, lin-4, was identified in a C. elegans mutant screen designed to identify genes involved in developmental timing [reviewed in 12]. Cloning and analysis revealed that lin-4 is a small RNA that does not encode a protein [5]. The lin-4 miRNA accumulates during the first and second larval stages and triggers passage to the third larval stage by repressing the translation of at least two genes, lin-14 and lin-28 [13]. The activity of lin-4 depends on the partial homology of the miRNA to specific regions of the 3' untranslated regions (UTRs) of lin-14 and lin-28 mRNAs [5, 14]. Additional miRNAs have been functionally characterized (Figure 2). The range of miRNA functions affect early stage development, cell differentiation, and cell death, illustrating the critical roles that miRNAs play in cellular biology.


Figure 2. Function of Known miRNAs in Plants, Mouse, Fly, and Worm.

In animals, miRNAs are partially homologous to their mRNA targets. Using similar target selection criteria, a number of labs have predicted the mRNAs that miRNAs bind and regulate [15, 16]. Some of these putative miRNA target sites have been verified by monitoring target protein expression and using reporter constructs [15, 16].

Three critical points about miRNA function are:

(1) Each miRNA appears to regulate the translation of multiple gene
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