Reverse transcriptase is an enzyme that synthesizes DNA from an RNA template. It is an RNA‑dependent DNA polymerase that converts single‑stranded viral RNA into complementary DNA (cDNA), enabling integration into the genome.
Structure and Function
First identified in the early 1970s in oncogenic RNA tumor viruses, reverse transcriptase became a cornerstone of the central dogma revision. The enzyme possesses both RNA‑dependent DNA polymerase and ribonuclease H activities. During retroviral replication, reverse transcriptase uses a cellular tRNA as a primer to initiate synthesis of a complementary DNA strand from the viral RNA genome. The RNase H domain degrades the RNA template as it is copied, and the polymerase domain synthesizes a second DNA strand to form a double‑stranded DNA intermediate. This double‑stranded DNA is transported into the nucleus and integrated into the host genome. Reverse transcriptases lack proofreading exonuclease activity, so they make frequent errors, contributing to the rapid evolution of retroviruses such as HIV. Homologous enzymes are present in retrotransposons and the telomerase complex, which uses its own RNA template to extend chromosome ends.
Applications and Inhibitors
Reverse transcriptase has been harnessed in molecular biology to generate complementary DNA for cloning, gene expression studies and quantitative PCR. Reverse transcription polymerase chain reaction (RT‑PCR) combines cDNA synthesis with amplification to detect and quantify RNA transcripts. In medicine, reverse transcriptase is a major target of antiretroviral therapy; nucleoside and non‑nucleoside reverse transcriptase inhibitors interrupt viral DNA synthesis in HIV‑infected cells. Drugs such as zidovudine, lamivudine and efavirenz bind the enzyme’s active site or allosteric sites, suppressing viral replication. Because retroviruses rely on reverse transcription for replication, the enzyme remains central to understanding viral evolution and developing treatments.
Reverse transcriptase links RNA and DNA synthesis and illustrates the fluidity of genetic information flow. Its discovery reshaped basic biology, and its unique enzymatic activities have been exploited in research and targeted in antiviral therapy.
Related Terms: Retrovirus, cDNA, RNA‑dependent DNA polymerase, Telomerase, RT‑PCR