4 Strong-stop Strand Transfer during Reverse Transcription

Abstract

Reverse transcription of retroviral genomic RNA is, in a sense, a discontinuous process. The production of each strand of integration-competent retroviral DNA begins with the synthesis of short, discrete DNA products that can be elongated only after they are moved to secondary template locations in a process called strand transfer. Both strand transfers during reverse transcription involve the translocation of short DNA products from their sites of synthesis at one end of the genome to acceptor template regions at the other end of the genome, where DNA synthesis resumes. Because of the strand-transfer reactions, the final product of reverse transcription is a linear double-stranded DNA molecule that is longer at each end than the RNA from which it was duplicated. The termini of the completed viral DNA consist of identical sequences termed long terminal repeats (LTRs), which are formed when information present near the ends of the genomic RNA is duplicated at the tips of the preintegrative DNA. The conservation of the two-LTR structure in all retroviruses and among other retroelements whose life cycles involve an integrated DNA form, such as yeast Tys and Drosophila copia elements, suggests that the process of strand transfer is as conserved a feature of these elements’ replication as the process of reverse transcription itself. Strand transfer, as a specialized form of template switching, is mechanistically related to some models for recombination during reverse transcription. Thus, the mechanisms for strong-stop strand transfer and for the generation of retroviral genetic diversity through recombination and transduction of...