miRNA, siRNA, piRNA: Knowns of the unknown.

RNA silencing is a common term for a group of mechanistically related pathways that produce and employ short non-coding RNA molecules to achieve sequence-specific gene regulation. The RNase III-enzyme Dicer produces small RNAs (smRNAs) in both microRNA (miRNA) and RNA interference (RNAi) pathways. miRNAs modulate physiological and developmental gene expression. They are genome-encoded, endogenous negative regulators of translation and mRNA stability originating from long primary transcripts with local hairpin structures. RNAi is triggered by the processing of long double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs), which mediate sequence-specific cleavage of nascent mRNAs. The third common class of repressive small RNAs, PIWI-associated RNAs (piRNAs), is produced in a Dicer-independent manner. Current data suggest that piRNAs protect the germline from mobile genome invaders such as transposons. A small RNA involved in RNA silencing associates with proteins in an effector ribonucleoprotein complex usually referred to as RNA-Induced Silencing Complex (RISC). Key components of RISC complexes are proteins of the Argonaute family, which determine RISC functions. During three days in May 2008, around two hundred scientists working on RNA silencing met at IMBA, Vienna for the 3(rd) Microsymposium on Small RNAs (Fig. 1) (www.imba.oeaw.ac.at/microsymposium) organized by Javier Martinez.