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Most microRNAs (miRNAs) are processed by two ribonuclease III enzymes. The first cleavage is performed by Microprocessor that is composed of RNase III enzyme Drosha and DGCR8, and the second by another RNase III enzyme Dicer. There are many examples of miRNAs that are poor substrates for Drosha and Dicer, owing to their suboptimal structures. However, a number of these suboptimal miRNAs are known to be expressed at the same or higher level as their neighboring structurally-optimal miRNAs. Recent studies suggest that the clustered orientation of these suboptimal miRNAs is the explanation for this phenomenon. It has been observed that the biogenesis of these suboptimal miRNAs can be affected by the expression of their neighboring optimal miRNAs. This principle is expected to apply more broadly, as it has been shown that a large percentage of suboptimal miRNAs reside within operons.

MicroRNA clustering on the biogenesis of suboptimal microRNAs