Retrovirus genome replication: priming specificities of plus-strand DNA synthesis

The retroviral reverse transcriptase is a multifunctional protein. Not only does it contain both RNA- and DNA-directed DNA synthesis activities but also it contains an endonuclease activity necessary for the integration of viral RNA and a RNase H. This latter activity can reduce to oligoribonucleotides viral RNA that has been reverse transcribed into minus-strand DNA. However, during avian retrovirus genome replication it does this in a highly specific manner so as to generate a specific 12-base primer for plus-strand DNA synthesis. Even though many other oligoribonucleotides are also made there is an efficient selection of the specific primer followed by its efficient utilization in plus-strand DNA synthesis, and subsequent removal. We have used a reconstructed system to gain an understanding of the factors that contribute towards these observed specificities.