Reverse transcriptase

Reverse transcriptases (RT), and RNA -dependent DNA polymerases are enzymes catalyzing the transcription of RNA into DNA. To synthesize a first single-stranded RNA of an RNA -DNA hybrid strand by a RNA-dependent DNA polymerase activity. For the subsequent degradation of the RNA portion in a separate section of the protein is responsible, of the RNase H component. It follows the completion of the single - to double-stranded DNA strand by a DNA-dependent DNA polymerase.

History

The reverse transcriptase was described in 1970 by Howard Temin and both also independently by David Baltimore for the first time. In 1975, she received the Nobel Prize in Physiology or Medicine for this discovery together with Renato Dulbecco. The addition of reverse by the particular assets of this enzyme, reverse the usual process direction of transcription and establish a DNA using a RNA template. With this discovery, which until then represented doctrine was rejected, that the information flow can always extend only in the direction of DNA → RNA → protein and never vice versa.

Occurrence

The reverse transcriptase was first discovered in retroviruses ( eg HIV, HTLV, SIV ). These viruses with RNA genome using RT to rewrite their genome into DNA. The RT therefore fulfills a crucial role in the propagation of the virus. In addition, certain DNA viruses such as the hepadnaviruses (for example, the causative agent of hepatitis B (HBV), or the caulimoviruses which occur in plants ) containing a RT. From former mutant retroviruses also the class I transposons, retroelements also originate called from. They require a RT for its replication. This is either by themselves coded ( autonomous LINEs and LTR retrotransposons ) or must be provided ( eg SINEs ).

A reverse transcriptase is also a component of telomerase in eukaryotes, where it extends the shortened telomeres in the course of replication back to the original length, and thus delays the process of cell aging. The more accurate term is telomerase reverse transcriptase ( TERT ), such as for the human telomerase reverse transcriptase ( hTERT).

Biotechnological applications

The error rate of the viral reverse transcriptase is due to a missing correction function ( proof-reading ) at 1:103 to 1:104 and leads to a very high mutation rate, which complicates the fight against retroviruses such as HIV. Inhibiting the reverse transcriptase is an object of the combination therapy and different drugs (NNRTI, NRTI) possible. Such reverse transcriptase inhibitors were the first, and until 1994 only approved for the treatment of HIV infection effective drugs.

Reverse transcriptases can be used in molecular biology and molecular diagnostics, to create, for example, in the RT-PCR, or a cDNA library. For this, the viral reverse transcriptases from murine leukemia virus (MLV ) or the avian myeloblastosis virus ( AMV ) are used.

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