Expanding RNA physiology: microRNAs in a unicellular organism

Until recently, the world viewed through the eyes of molecular biologists seemed simple with a well-known slogan hailing a central dogma: “DNA makes RNA makes protein.” This has been interpreted to mean that genetic output is entirely or almost entirely transacted by proteins (Mattick 2004). However, within a few years of the discovery of RNA interference (RNAi) (Fire et al. 1998), an explosion of data has lifted the veil off many previous puzzling findings. Thus, our view of the field was irrevocably changed with a new slogan—that went alongside the classical central dogma—“RNA makes small RNA makes no protein” (Fig. 1). Sequence information in long RNA transcripts is converted into small, ∼20- to 30-nucleotide (nt)-long, non-protein-coding RNAs such as microRNAs (miRNAs) and small interfering RNAs (siRNAs). These small RNAs trigger various forms of sequence-specific gene silencing, including RNA cleavage and degradation, cleavage-independent mRNA decay, translational repression, methylation of protein-coding DNA, and heterochromatin formation in a variety of eukaryotic organisms ranging from fission yeast, plants, fungi, nematode, and fly to humans. This process is now collectively referred to as RNA silencing (Tomari and Zamore 2005; Zaratiegui et al. 2007). In addition to classical small non-protein-coding RNAs—including tRNAs, small nuclear RNAs (snRNAs), and small nucleolar RNAs (snoRNAs)—recent studies have shown that our cells express a surprisingly large number of new regulatory small RNAs that seem to be particularly abundant in roles that direct the binding of protein complexes to specific nucleic acid sequences (Hüttenhofer and Schattner 2006). These include miRNAs, several groups of natural or endogenous siRNAs, and Piwi-interacting RNAs (piRNAs) (Kim 2006). The ongoing efforts to uncover the full biological scope of RNA silencing have already modified our notions about how gene expression is controlled. It is becoming clear that RNA silencing comprises an important tier of gene expression in …