August 8, 2022

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Human cells can write RNA sequences into DNA and challenge is coming!

Human cells can write RNA sequences into DNA and challenge is coming!

 

 

Human cells can write RNA sequences into DNA and challenge is coming!  Rewrite the textbook! Human cells can write RNA sequences into DNA, and the central law of the basic laws of life is challenged!


The basic law of modern life science, the “central law”, points out the direction of the flow of genetic information. Except for a very small number of retroviruses, genetic information goes from DNA to RNA, RNA to protein. The DNA polymerase responsible for this unidirectional flow of genetic information cannot reverse RNA back to DNA. However, a recent study found for the first time evidence that human DNA polymerase reverses RNA back to DNA. This is undoubtedly a subversion of the central principle. .

On April 25, 1953, James Watson, Francis Crick and others uncovered the double helix structure of DNA and ushered in the era of molecular genetics.

Human cells can write RNA sequences into DNA and challenge is coming!

In 1958, Francis Crick, one of the discoverers of the DNA double helix structure, first proposed the central law. Today, the central law has become the most important and basic law of life sciences.

The central law indicates the flow direction of genetic information: DNA→DNA (self-replication of DNA), DNA→RNA (transcription), RNA→protein (translation). The vast majority of life on earth follow this rule. For RNA viruses, some of them have RNA→RNA (RNA self-replication), and for retroviruses in RNA viruses, there is RNA→DNA (reverse transcription). .

Central Rule

 

In 1982, Stanley Prusiner successfully isolated the pathogen that causes Creutzfeldt-Jakob disease and named it Prion (prion). However, prions are composed of only proteins and do not contain any DNA. And RNA, but it can self-replicate and spread diseases, which seems obviously not in line with the central law. Is the theoretical cornerstone of life sciences crumbling?

In 1991, 9 years after the discovery of prions, Bruchner successfully elucidated the pathogenic mechanism of prions. Prions are essentially infectious special proteins. Prions (SC-type PrP-type proteins) come into contact with normal C-type PrP proteins in the organism, causing C-types to become SC-types, which are replicated in batches through protein allostery. Yourself.

Therefore, prions are still encoded by genes, and they can realize self-replication and spread diseases by changing the conformation of the normal PrP protein. This also means that the theoretical cornerstone of modern life science-the central law, does not need to be revised.

The central law explains the flow of genetic information from self-replicating DNA to RNA and from RNA to protein. So far, polymerases, the key molecular machinery that determines the unidirectional flow of genetic information, have been considered unable to write RNA as DNA information.

However, recently, researchers from Thomas Jefferson University and the University of Southern California published a research paper titled: Polθ reverse transcribes RNA and promotes RNA-templated DNA repair in Science Advances, a sub-issue of the top international academic journal Science.

The study found that human DNA polymerase θ (Polθ) can efficiently compile RNA information into DNA. This discovery challenges the basic law of life science-the central law, which means that there is Polθ-mediated in human cells. The reverse flow of genetic information from RNA to DNA.

The results of this study have a more far-reaching impact: Will the currently widely vaccinated mRNA vaccine be reverse-transcribed into DNA under the action of Polθ?

Human cells can write RNA sequences into DNA and challenge is coming!

 

Among the 14 DNA polymerases in mammalian cells, only 3 are responsible for completing the genome replication before cell division. The remaining 11 polymerases are mainly responsible for checking various errors in DNA and repairing them.

DNA polymerase θ (Polθ) is responsible for this kind of DNA repair work, but its work is not done well, and it often leads to errors and mutations during repair. This made researchers notice the similarities between it and the reverse transcriptase of retroviruses.

The reverse transcriptase of the retrovirus HIV can act as a DNA polymerase like Polθ, but it can also bind RNA and turn it back into the DNA chain, which is the reverse transcription process in retroviruses.

Because Polθ is error-prone and confusing, and contains an inactive proofreading domain, the research team decided to test whether it has the ability to synthesize DNA from RNA templates.

Experimental results show that Polθ can convert RNA information into DNA. It is comparable to HIV virus reverse transcriptase in synthesizing DNA from RNA, and surpasses reverse transcriptase in replicating DNA.

Human cells can write RNA sequences into DNA and challenge is coming!


The research team confirmed that Polθ is more effective and accurate when using RNA templates to write DNA information than when copying DNA, indicating that the former may be its main cell function.

Next, Richard Pomerantz, the corresponding author of the study, collaborated with Professor Xiaojiang Chen of the University of Southern California, using the knowledge of X-ray crystallography in Chen Xiaojiang’s laboratory to analyze the crystal structure of Polθ. It was found that Polθ is similar to the reverse transcriptase of retroviruses, undergoing major structural changes to adapt to the type A DNA/RNA hybrid, and forming multiple hydrogen bonds with the template ribose hydroxyl group.

Human cells can write RNA sequences into DNA and challenge is coming!

 

It is worth mentioning that Polθ is only expressed in a few tissue types, but it is highly expressed in many cancer cells, and the presence of Polθ corresponds to a poor clinical outcome. Polθ can confer resistance to cancer therapy and promote lack of DNA Survival of abnormal cells in damage repair pathways.


In general, the results of this study indicate that the main function of DNA polymerase θ (Pol θ) is to act as a reverse transcriptase. In healthy cells, Pol θ acts as RNA-mediated DNA repair. In cancer cells, Polθ is highly expressed, and promotes and promotes cancer cell growth and drug resistance.

 

This study reveals the activity of DNA polymerase θ (Polθ) on RNA and how it promotes DNA repair and cancer cell proliferation. This not only challenges the basic law of life science, “the central law”, but also suggests that Polθ is a promising Anti-cancer drug targets.

 

In addition, since DNA polymerase θ (Polθ) can use RNA as a template to compile DNA information, will the widely vaccinated mRNA vaccines have a far-reaching impact that is currently unknown?

 

(source:internet, reference only)


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