reversetranscriptase

Reverse transcriptase (RT) is an RNA-dependent DNA polymerase that copies RNA into DNA. It occurs in retroviruses, certain cellular enzymes such as telomerase, and some retrotransposons. RT enzymes typically synthesize DNA from an RNA template and possess RNase H activity that degrades the RNA strand of RNA–DNA hybrids during replication. In many retroviral RTs the polymerase active site includes a conserved YMDD motif; HIV-1 RT is a well-known example that functions as a heterodimer of p66 and p51 subunits.

Biological role and diversity: In retroviruses, RT converts the viral genome into DNA suitable for integration into the host genome. Telomerase uses reverse transcription to extend chromosome ends, while various retroelements encode RTs contributing to genome evolution. RTs are generally error-prone, contributing to mutation rates in viral populations; fidelity and processivity vary among enzymes. Structural differences include single-subunit and heterodimeric forms, and variations in RNase H activity and thermostability.

Applications and inhibitors: In molecular biology, RT enzymes synthesize complementary DNA (cDNA) from RNA for cloning, sequencing, and quantitative assays such as RT‑PCR and RT‑qPCR. Common lab RTs derive from Moloney murine leukemia virus (M‑MLV) or avian myeloblastosis virus (AMV). In medicine, RT is targeted by antiretroviral drugs: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) terminate DNA synthesis, while non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit RT through allosteric mechanisms.

History: The discovery of reverse transcription was made independently by Temin and Baltimore in the 1960s–1970s, leading to the 1975 Nobel Prize in Physiology or Medicine. RT remains central to both virology and molecular biology.