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23 The Genomic Tag Hypothesis: Modern Viruses as Molecular Fossils of Ancient Strategies for Genomic Replication

Nancy Maizels, Alan M. Weiner


tRNA Plays a Surprising Number of Roles in Replication
First impressions are often lasting, and it is probably safe to say that most molecular biologists first encounter tRNA as a key component of the translation machinery. This is how tRNA is presented in elementary courses, and this is how the molecule is portrayed in textbooks. Yet because tRNA is commonly introduced as a component of the translation machinery, it is all too easy to come to think of translation as the primary or proper function of tRNA. In fact, as we discuss in detail, tRNA and tRNA-like molecules also play key roles in a wide variety of replicative processes, including replication of single-stranded RNA viruses of bacteria, plants, and possibly mammals; replication of duplex DNA plasmids of fungal mitochondria; retroviral replication; and replication of modern chromosomal telomeres.

How did tRNA come to have so many different roles in replication? One possibility is that, for reasons which are not yet understood, tRNA or tRNA-like structures have been repeatedly and independently borrowed from translation to serve ad hoc roles in replication. Alternatively, tRNA or tRNA-like structures may be widespread in contemporary replication because tRNA played a central role in the replication of ancient RNA genomes, a role which has been conserved as well as subtly transformed as genomes evolved from RNA to duplex DNA.

We have proposed that tRNA-like structural motifs first evolved as 3′ -terminal structures that tagged RNA genomes for replication in the RNA world before the advent of...

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