Although tRNA is best known as a component of the translation apparatus, tRNA and tRNA-like molecules also play key roles-either as template or as primer-in a wide variety of replicative processes. These processes include replication of single-stranded RNA viruses of bacteria, plants, and possibly mammals; replication of duplex DNA plasmids of fungal mitochondria; replication of retroviral and pararetroviral genomes; and replication of modern chromosomal telomeres. Consider the following two obvious examples. First, the 3' end of many eubacterial and plant single-stranded RNA viruses resembles the "top half" (acceptor stem/loop) of tRNA, with a stem/loop structure immediately followed by the 3' terminal sequence CCA. This tRNA-like structure functions as the template for initiation of RNA replication. In fact, some of these tRNA-like structures are so similar to bona fide tRNA that they can be aminoacylated by the corresponding aminocyl-tRNA synthetases. Second, the replication of most retroviral RNA genomes begins with annealing of a mature tRNA to the primer binding site on genomic RNA; reverse transcriptase then uses the tRNA as primer to copy the RNA genome into the first strand of DNA. Thus in each case tRNA or a tRNA-like structure plays a role in initiation of RNA replication, but in one instance it functions as template and in the other as primer. Is this pure coincidence, or does it suggest descent from a common ancestral function? No conclusions could be drawn from just two examples, but many more instances are known in which tRNA plays a role in replication, and many of these examples appear to provide "missing links," or connections, between one replicative strategy and another.
