Reverse transcriptase
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2008-05-30T14:15:15Z
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|Name=Reverse Transcriptase
|Photo=1HMV.png|250px
|Caption=3D model of [[HIV]] reverse transcriptase
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|Names=Deoxynucleoside-triphosphate:<br>DNA deoxynucleotidyltransferase (RNA-directed)<br>
*RNA-directed DNA polymerase
*DNA nucleotidyltransferase (RNA-directed)
*Revertase
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|ECnumber = 2.7.7.49
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In [[biochemistry]], a '''reverse transcriptase''', also known as '''RNA-dependent DNA polymerase''', is a [[DNA polymerase]] [[enzyme]] that [[transcription (genetics)|transcribes]] single-stranded [[RNA]] into double-stranded [[DNA]]. Normal transcription involves the synthesis of RNA from DNA; hence, reverse transcription is the ''reverse'' of this.
Reverse transcriptase was discovered by [[Howard Temin]] at the [[University of Wisconsin-Madison]], and independently by [[David Baltimore]] in 1970. The two shared the 1975 [[Nobel Prize in Physiology or Medicine]] with [[Renato Dulbecco]] for their discovery.
Well studied reverse transcriptases include:
* HIV-1 reverse transcriptase from [[HIV|human immunodeficiency virus]] type 1 ({{PDB|1HMV}})
* M-MLV reverse transcriptase from the [[murine leukemia virus|Moloney murine leukemia virus]]
* AMV reverse transcriptase from the [[Alpharetrovirus|avian myeloblastosis virus]]
* [[Telomerase|Telomerase reverse transcriptase]] that maintains the [[telomere]]s of [[eukaryotic]] [[chromosomes]]
==Function==
===Viruses===
The enzyme is encoded and used by [[Virus classification|reverse-transcribing viruses]], which use the enzyme during the process of replication. Reverse-transcribing [[RNA virus]]es, such as [[retrovirus]]es, use the enzyme to reverse-transcribe their RNA genomes into DNA, which is then integrated into the host genome and replicated along with it. Reverse-transcribing [[DNA virus]]es, such as the [[hepadnavirus]]es, transcribe their genomes into an RNA intermediate and then, using reverse transcriptase, back into DNA.
===Eukaryotes===
Self-replicating stretches of [[eukaryotic]] genomes known as [[retrotransposon]]s utilise reverse transcriptase to move from one position in the genome to another via a RNA intermediate. They are found abundantly in the genomes of plants and animals. [[Telomerase]] is another reverse transcriptase found in many eukaryotes, including humans, which carries its own [[RNA]] template; this RNA is used as a template for [[DNA replication]]<ref>Lodish, et al, ''Molecular Cell Biology'' (2004), 5th edn, W. H. Freeman and Company, New York, ISBN 0-7167-4366-3</ref>.
===Prokaryotes===
Reverse transcriptases are also found in bacterial [[retron]]s, distinct sequences which code for reverse transcriptase, and are used in the synthesis of [[multicopy single-stranded DNA|msDNA]].
==Structure==
Reverse transcriptase enzymes include an RNA-dependent [[DNA polymerase]] and a DNA-dependent DNA polymerase, which work together to perform transcription. In addition to the transcription function, retroviral reverse transcriptases have a domain belonging to the [[RNase H]] family which is vital to their replication.
==Replication fidelity==
Reverse transcriptase has a high error rate when transcribing RNA into DNA since, unlike [[DNA polymerase]]s, it has no [[proofreading]] ability. This high error rate allows [[mutation]]s to accumulate at an accelerated rate relative to proofread forms of replication. The commercially available reverse transcriptases produced by [[Promega]] are quoted by their manuals as having error rates in the range of 1 in 17,000 bases for AMV and 1 in 30,000 bases for M-MLV<ref>[http://www.promega.com/pnotes/71/7807_22/7807_22_core.pdf Promega kit instruction manual (1999)]</ref>
==Applications==
[[Image:Zidovudine.svg|thumb|200px|The molecular structure of [[zidovudine]] (AZT), a drug used to inhibit [[HIV]] reverse transcriptase]]
===Antiviral drugs===
{{details|Reverse transcriptase inhibitor}}
As [[HIV]] uses reverse transcriptase to copy its genetic material and generate new viruses (part of a retrovirus proliferation circle), specific drugs have been designed to disrupt the process and thereby suppress its growth. Collectively, these drugs are known as [[reverse transcriptase inhibitor]]s and include the nucleoside and nucleotide analogues [[zidovudine]] (trade name Retrovir), [[lamivudine]] (Epivir) and [[tenofovir]] (Viread), as well as non-nucleoside inhibitors, such as [[nevirapine]] (Viramune).
===Molecular biology===
{{details|Reverse transcription polymerase chain reaction}}
Reverse transcriptase is commonly used in research to apply the [[polymerase chain reaction]] technique to [[RNA]] in a technique called [[reverse transcription polymerase chain reaction]] (RT-PCR). The classical [[polymerase chain reaction|PCR]] technique can only be applied to [[DNA]] strands, but with the help of reverse transcriptase, RNA can be transcribed into DNA, thus making [[Polymerase chain reaction|PCR]] analysis of RNA molecules possible. Reverse transcriptase is also used to create [[cDNA library|cDNA libraries]] from [[mRNA]]. The commercial availability of reverse transcriptase greatly improved knowledge in the area of molecular biology as, along with other enzymes, it allowed scientists to clone, sequence and characterise DNA.
==See also==
*[[cDNA library]]
*[[DNA polymerase]]
*[[msDNA]]
*[[Reverse transcribing virus]]
*[[RNA polymerase]]
*[[Telomerase]]
*[[Retrotransposon marker]]
==External links==
*[http://www.tibotec.com/bgdisplay.jhtml?itemname=HIV_discovery&product=none&s=2 animation of reverse transcriptase action and three reverse transcriptase inhibitors]
*[http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb33_1.html Molecule of the month] (September 2002) at the [[Protein Data Bank]]
*[http://www.brenda.uni-koeln.de/php/result_flat.php4?ecno=2.7.7.49 BRENDA database entry] - highly detailed information from a protein database
* {{MeshName|RNA+Transcriptase}}
* {{EC number|2.7.7.49}}
==References==
{{reflist}}
{{Kinases}}
[[Category:EC 2.7.7]]
[[Category:Molecular biology]]
[[Category:Viral enzymes]]
[[da:Revers transkriptase]]
[[de:Reverse Transkriptase]]
[[es:Transcriptasa inversa]]
[[fr:Transcriptase inverse]]
[[ko:역전사효소]]
[[it:DNA polimerasi (RNA-dipendente)]]
[[he:רוורס טרנסקריפטאז]]
[[lt:Atvirkštinė transkriptazė]]
[[nl:Reverse-transcriptase]]
[[ja:逆転写酵素]]
[[pl:Odwrotna transkryptaza]]
[[pt:Transcriptase reversa]]
[[ru:Обратная транскриптаза]]
[[sv:Omvänt transkriptas]]
[[ur:معکوس انتساخہ]]
[[zh:逆轉錄酶]]