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Reverse Transcriptase
The discovery of retroviral reverse transcriptases (RTs) in 1970 represented a major breakthrough with an enormous impact on life sciences. These enzymes were described as nucleic acid polymerases able to synthesize a complementary DNA (cDNA) using RNA as template. RTs were able to use RNA or DNA as templates and had ribonuclease H (RNase H) activity. The RNase H activity of the RTs facilitates cleavage of the RNA strand when forming part of RNA/DNA heteroduplexes. Reverse transcription (i.e. the conversion of RNA to DNA by an RT) plays an important role in the replication of Retroviridae, Metaviridae, Pseudoviridae, Hepadnaviridae and Caulimoviridae. RTs encoded in their genomes are phylogenetically related to those found in mobile genetic elements of prokaryotes and eukaryotes.
Amino acid sequence alignments of RT DNA polymerase domains of different clades show the conservation of a series of motifs, required for enzymatic function. The role of RTs in the replication of retroviruses (then known as ‘RNA tumor viruses’) gave them notorious relevance for understanding malignant transformation. In plants and animals, RT activity is associated with the replication of chromosome ends (telomerase). In prokaryotes, RTs have been found in the coding region of an extrachromosomal satellite DNA, known as multicopy single-stranded DNA (msDNA) and in mobile genetic elements known as group II introns that contain an N-terminal RT (RNA-dependent DNA polymerase) domain followed by an RNA-binding maturase domain. Despite the important similarities between RTs of different viruses, efforts have been devoted to understanding the mechanism of reverse transcription in retroviruses, and the structure of human immunodeficiency virus type 1 (HIV-1) RT as a target of antiretroviral therapy.1.Menéndez-Arias L,et al. Virus Res. 2017;234:153–176.
Amino acid sequence alignments of RT DNA polymerase domains of different clades show the conservation of a series of motifs, required for enzymatic function. The role of RTs in the replication of retroviruses (then known as ‘RNA tumor viruses’) gave them notorious relevance for understanding malignant transformation. In plants and animals, RT activity is associated with the replication of chromosome ends (telomerase). In prokaryotes, RTs have been found in the coding region of an extrachromosomal satellite DNA, known as multicopy single-stranded DNA (msDNA) and in mobile genetic elements known as group II introns that contain an N-terminal RT (RNA-dependent DNA polymerase) domain followed by an RNA-binding maturase domain. Despite the important similarities between RTs of different viruses, efforts have been devoted to understanding the mechanism of reverse transcription in retroviruses, and the structure of human immunodeficiency virus type 1 (HIV-1) RT as a target of antiretroviral therapy.1.Menéndez-Arias L,et al. Virus Res. 2017;234:153–176.