Role of MicroRNA in Pancreatic β-Cells

Where More Is Less

One of most intriguing discoveries in biology in recent years is unquestionably the identification of the family of small, noncoding RNAs known as microRNAs (miRNAs). Originally described in worms (1), miRNAs are now known to be virtually ubiquitous among vertebrates, including humans. Over 400 genes encoding miRNAs are dispersed throughout the human genome, many of them unexpectedly located within the borders of conventional, protein-coding genes (2). miRNA genes are transcribed primarily by RNA polymerase II into long precursor molecules that are processed via the RNase III enzymes Drosha and Dicer into the mature, ∼22-nucleotide miRNA (3,4).

Functional studies are beginning to reveal the involvement of miRNAs in a remarkable array of key cellular activities including differentiation, proliferation, and metabolic integration (5). Each miRNA targets multiple mRNA species through recognition of complementary sequences, typically located at multiple sites within the 3′ untranslated region. This results in reduction in the level of the corresponding protein, either through destabilization of the mRNA or inhibition of translation (3). The effects of each such interaction may be subtle, complicating the process of dissecting out these effects. Nevertheless, it is becoming abundantly clear that the miRNAs have a profound effect on controlling and integrating programs of gene expression. For example, miRNAs can act both upstream and downstream of key cellular transcription factors (6), thereby exerting broadly pleiotropic effects. Furthermore, evidence is now accumulating …