Small RNAs with big impacts

Although they are tiny, microRNAs can have large-scale effects because they regulate a variety of genes. These minuscule molecules are now definitively linked to the development of cancer.

During the past few years, molecular biologists have been stunned by the discovery of hundreds of genes that encode small RNA molecules1. These microRNAs (miRNAs) — 21 to 25 nucleotides in length — are negative regulators of gene expression. The mechanisms by which they work are similar in plants and animals, implying that they are involved in fundamental cellular processes2. As cancer is essentially a consequence of disordered genome function, one might expect these regulatory molecules to be involved in the development of this disease. Indeed, there are hints that the levels of some miRNAs are altered in cancer3, 4; there is also evidence that an miRNA regulates the cancer-promoting ras gene5. Three studies in this issue6, 7, 8 change the landscape of cancer genetics by establishing the specific miRNAs expressed in most common cancers, and investigating the effects of miRNAs on cancer development and cancer genes.

The initial product of an miRNA gene (Fig. 1) goes through several processing steps before it is exported from the nucleus to the cytoplasm. One strand of the resulting double-stranded RNA is then incorporated into the 'RNA-induced silencing complex' (RISC). RISC can target protein-coding messenger RNAs (mRNAs) either for inhibition, by blocking their translation into protein, or destruction (as in RNA interference). Base pairing between the miRNA and its complementary target mRNA gives the process its specificity.

http://www.nature.com/nature/journal/v435/n7043/full/435745a.html