What is the enzyme reverse transcriptase?
Reverse transcriptase (RT), also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into DNA.
This enzyme is able to synthesize a double helix DNA once the RNA has been reverse transcribed in a first step into a single-strand DNA
As laboratories worldwide rushed to develop reliable diagnostic tests for COVID-19, techniques using the enzyme became the gold standard to detect the SARS-2 virus, and a cornerstone of molecular diagnostics.
Significance & History
Researchers in the labs of Howard Temin and David Baltimore independently discovered it and published their findings in back-to-back articles in the journal Nature in 1970.
The prevailing belief at the time was that in all living beings, hereditary information flowed only from DNA to RNA and from RNA to protein (a.k.a. the ‘Central Dogma’).
The discoveries of Drs. Temin and Baltimore et al. showed information could flow the other way, too, with RNA giving ‘rise’ to DNA
The ability of cells to create DNA copies from RNA revolutionised research methods in molecular biology, where researchers could reverse-transcribe messenger RNAs to pieces of DNA, clone that DNA into bacterial vectors, and study the function of the corresponding genes
Impact on HIV/AIDS
In diagnostics, clinicians used reverse transcriptase to convert RNA to DNA and thus estimate the amount of viral material in a given sample.
This technique quickly found wide application and use in the study of RNA viruses, including hepatitis B and the human immunodeficiency virus (HIV).
The discovery of reverse transcriptase had a significant effect on the management and treatment of HIV infections, including Acquired Immunodeficiency Syndrome (AIDS), in 1980s.
A generation of antiviral agents that specifically targeted the reverse transcriptase enzyme helped convert an otherwise deadly disease to one that could be managed, translating to improving the long-term outcomes and survival of people living with AIDS.
Role in Human Genome and Evolution
The human genome is interspersed in many places with sequences, called elements, that appear to have originated from retroviruses. Thus, researchers call them retroelements
Recent evidence has suggested that these retroelements could really have had a profound impact on human biology and evolution, and that they play important roles in a variety of physiological processes
A recent journal, reported that the expression of more than a thousand human endogenous retroviruses — a major class of retroelements in the human genome — could be associated with a risk of neuropsychiatric diseases in humans.
Retroelements in the human genome and bacterial reverse transcriptases have a common evolutionary history as well as share functional mechanisms.
Bacterial reverse transcriptases — believed to be the precursors of their eukaryotic counterparts — exhibit analogous mechanisms.
The discovery of reverse transcriptase activity across the different domains of life underscores the enzyme’s fundamental role in both prokaryotic and eukaryotic systems as well as a remarkable evolutionary continuity and functional versatility
Biotechnological and Medical Applications
When the bacteria Klebsiella pneumoniae is infected by bacteriophages — viruses that infect bacteria — they use a non-coding RNA with specific motifs (or structures) that could bind to reverse transcriptase and instruct cells to create DNA.
This DNA copy has multiple copies of a gene that can create a specific protein.
The researchers dubbed this protein ‘Neo’ for “never-ending open-reading frame”.
It could place the bacterial cell in a state of suspended animation, blocking its replication, and thus stalling the replication of the invading bacteriophage as well.
Thus, the infection is stopped in its tracks
Recent discoveries hint at the potential of innovative applications in biotechnology and medicine, especially in the context of emerging antimicrobial resistance, the ability of disease-causing microbes to resist the effects of substances designed to incapacitate or kill them.
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