Small RNAs in development and disease

MicroRNAs (miRNAs) and short interfering RNAs (siRNAs) are classes of regulatory small RNA molecules, ranging from 18 to 24 nucleotides in length, whose roles in development and disease are becoming increasingly recognized. They function by altering the stability or translational efficiency of messenger RNAs (mRNAs) with which they share sequence complementarity, and are predicted to affect up to one-third of all human genes. Computer algorithms and microarray data estimate the presence of nearly 1000 human miRNAs, and direct examination of candidate miRNAs has validated their involvement in various cancers, disorders of neuronal development, cardiac hypertrophy, and skin diseases such as psoriasis. This article reviews the history of miRNA and siRNA discovery, key aspects of their biogenesis and mechanism of action, and known connections to human health, with an emphasis on their roles in skin development and disease.Learning objectivesAfter completing this learning activity, participants should be able to summarize the relevance of microRNAs in development and disease, explain the molecular steps of how small RNAs regulate their targets within the human cell, and discuss the role of small RNAs in the diagnosis and treatment of disease.