tRNA Structure Goes from L to λ

strate attachment nor exogenous signals to maintain active cell cycling (Winklbauer, 1986). This profound difference in how the extracellular environment controls cell proliferation in amphibian and mammalian cells may have significant implications for how proteins commonly associated with proliferative regulation may be used during early development. Phylogenetic analyses of the p53 family indicate that p63 was the original member of the family seen in invertebrates , whereas p53 makes its first appearance in chordates (Yang et al., 2002). Significantly, p53 arose In this issue of Cell, Ishitani et al. (2003) report, in a in vertebrates apparently in concert with the dominant crystal, a new L-like structure of tRNA designated as negative versions of p63 and p73, suggesting the possi-␭-form, where disruption of universal tertiary interac-bility that these gene products evolved to interact tions is compensated by interactions with an enzyme through common DNA binding sites. We know from that makes a base modification at the corner of the L. mouse knockouts of the p63 and p73 genes that both are critical for developmental processes (Yang et al., 2002). p63 is essential for the maintenance of stem cells The determination of the three-dimensional structure of for many epithelial tissues, including skin, breast, uro-transfer RNA was a landmark for modern biology (Kim thelia, and prostate. In contrast, p73 appears critical et al., 1974; Robertus et al., 1974). Instead of a linear for aspects of neurogenesis, pheromone signaling, and double-stranded helix, tRNA organizes itself into two reproduction, and the control of inflammatory responses. major domains that are oriented at right angles so as At least one immediate question that accompanies the to give an overall L shape. A dense network of universally evolution of p53 was its function: was it selected to conserved base-base and base-backbone tertiary inter-perform tumor suppression, or rather as an intermediary actions holds the corner or elbow of the L together. coordinating the p63 and p73 genes and their newly This L-shaped structure is now considered the standard evolved dominant negative isoforms? Did its develop-three-dimensional format for all tRNAs. Remarkably, a mental role naturally lead to tumor suppression for the paper in this issue presents a new structure where virtu-longer-lived vertebrates? Piccolo and colleagues do not ally all of these tertiary interactions are broken (Ishitani address these questions directly, but rather link p63 et al., 2003), but the resulting new structure is nonethe-with p53 in somatic cell TGF-␤ signaling …