RNA interference：The short answer
One way of seeing what a gene does is to block its messenger RNA and note the effects. New work should make the approach more broadly applicable.
RNA interference (RNAi) was discovered only a few years ago1, but many scientists find it hard to imagine life without it. Once the sequence of a gene is known, RNAi offers a quick and easy way to determine its function, and the technique is accessible to a scientist in a small lab, as well as to a consortium attempting to assign function to the genes of an entire chromosome2,3. But although RNAi is now routine in laboratories studying a wide range of organisms, its use in mammalian cells has been problematic. On page 494 of this issue4 Tuschl and colleagues describe research that paves the way for successful RNAi in mammalian cells.
Figure 1Mammalian cells have at least two pathways that compete for double-stranded RNA (dsRNA). In the RNAi, or sequence-specific, pathway (blue arrows), the initiating dsRNA is first broken into short interfering (si) RNAs. siRNAs have sense and antisense strands of about 21 nucleotides that form 19 base pairs to leave overhangs of two nucleotides at each 38 end. siRNAs are thought to provide the sequence information that allows a specific messenger RNA to be targeted for degradation. The nonspecific pathway (red arrow) is triggered by dsRNA of any sequence, as long as it is at least 30 base pairs long. The nonspecific effects occur because dsRNA activates two enzymes: PKR, which in its active form phosphorylates the translation initiation factor eIF2a to shut down all protein synthesis, and 28, 58 oligoadenylate synthetase (28, 58-AS), which synthesizes a molecule that activates RNase L, a nonspecific enzyme that targets all mRNAs. The nonspecific pathway represents a host response to stress or viral infection; in the second case, the activating dsRNA is thought to derive from viral replication.
