RTs exhibit three key enzyme activities ( Fig. HIV RT is one of the most extensively studied polymerases in the context of understanding the biology of this devastating virus and designing RT inhibitors as drugs to manage HIV infections. Historically, the discovery of RT revolutionized molecular biology leading to the revision of the central dogma and enabling scientists to develop new research tools that heavily influenced cloning, analysis of gene expression and RNA biology. The enzyme telomerase maintaining the ends of the eukaryotic chromosomes is technically also a reverse transcriptase, although its mechanism is very distinct from conventional RTs. In addition, RTs are coded by dsRNA viruses that utilize reverse transcription such as hepatitis B virus (replication of hepatitis is discussed in Chapter 1) and various retroelements in eukaryotes and prokaryotes. Reverse transcriptases (RTs) are RNA dependent DNA pols initially isolated from retroviruses. It can use a 3′-hydroxyl end from any RNA or DNA molecule to prime its reaction without the need of any complementarity between the primer and the template. The Bombyx mori retrotransposon R2 also encodes a reverse transcriptase with unusual enzymatic properties. This mechanism protects the 3′ end of the transposon DNA from degradation by cellular exonucleases. Another unique feature of this enzyme is its ability to add one or two nucleotides to the 3′-terminal end of the DNA copy in a template-independent fashion. The Schizosaccharomyces pombe Tf1 transposon reverse transcriptase initiates DNA synthesis from an 11-nt RNA primer generated by self-annealing of the 11 terminal bases of the RNA genome to a complementary sequence located within the 5′ end and subsequently cleaved by its RNAse H activity to generate the 3′-hydroxyl end of the primer. Some of these elements encode reverse transcriptases with special properties. Similarly to retroviruses, their genomes possess the gene for reverse transcriptase, RNase H, and protease, but they lack the genes for the proteins of the viral capsid, so they do not generate virions and therefore do not spread among individuals, but are genetically inherited by the descendants if present in the chromosomes of germline cells. ![]() Retrotransposons are genetic mobile elements that utilize reverse transcription to generate a DNA copy of themselves to be inserted into eukaryotic genomes. Maga, in Brenner's Encyclopedia of Genetics (Second Edition), 2013 Reverse Transcriptase and Retrotransposons
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