Small silencing RNAs

Just fourteen years ago, Victor Ambros and coworkers discovered the first microRNA (miRNA). And just eight years ago, small interfering RNAs (siRNAs), the small silencing RNAs that mediate RNA interference (RNAi), were identified and subsequently shown in animals to be derived from a longer double-stranded RNA trigger and to serve as guides for the destruction of complementary mRNAs. The discovery of siRNAs enabled the application of RNAi — itself discovered in plants in 1990 and in animals in 1995 — to mammals, much as the identification in 1998 of double-stranded RNA as the trigger of RNAi enabled the widespread use of RNAi in other animals. Today, tens of thousands of small silencing RNAs have been identified, generating an alphabet soup of small silencing RNA types and sub-types. Small silencing RNAs have captivated the scientific world — bringing new genetic tools to model organisms, new explanations for regulatory interactions, new methods to pharmaceutical discovery, and new life to the biotechnology industry (where young start-up companies strive to develop siRNA-based drugs). They have even generated unprecedented discussion in the popular press: the cover of the international business magazine, the Economist, recently proclaimed small RNAs to be “Biology’s Big Bang”. For those of us in the RNA silencing field, the rapid progress in understanding the mechanisms and functions of small silencing RNAs and the accelerating discovery of new classes of tiny RNA silencers has been exhilarating. Despite their functional and biological diversity, all small Primer silencing RNAs function bound to a member of the Argonaute family of proteins. Through their association with Argonaute proteins, small RNAs take on unique properties that allow them to regulate diverse biological processes. Here, we shall consider the three dominant classes of animal small silencing RNAs: miRNAs, siRNAs and PIWIinteracting RNAs (piRNAs; Figure 1).