Human cells would be able to convert RNA sequences back into DNA, a function never identified until now.
- Cells are able to duplicate DNA to other cells through polymerases which can also duplicate it into RNAs.
- Researchers have discovered that certain polymerases are able to do the reverse and convert RNA into DNA.
- In unhealthy cells, cancer cells for example, these polymerases could promote the growth of cancer cells and resistance to treatment.
The relationship between DNA and RNA is becoming clearer. Until then, various scientific studies confirmed that DNA can influence RNA, but not the other way around. In new research, published June 11 in the journal Science Advances, American researchers from Thomas Jefferson University in Philadelphia, Pennsylvania, suggest that RNA segments can be rewritten into DNA. “This work opens the door to many more studies that will help us understand the importance of having a mechanism to convert RNA messages into DNA in our own cells.”, rejoiced Richard Pomerantz, associate professor of biochemistry and molecular biology at Thomas Jefferson University and lead author of the study.
The role of the polymerases in question
Human cells are able to duplicate DNA in new cells. This mechanism is possible thanks to what are called polymerases, which are enzymes that make it possible to replicate DNA. The latter also create RNA messages, which are transient copies of a portion of DNA, which are transported to transmit the information coded in our genome and allow the synthesis of proteins necessary for the functioning of our cells. Polymerases were thought to only work one way from DNA to DNA or RNA, preventing RNA messages from being written back into DNA.
That assumption is challenged by this new research which provides evidence, the researchers say, that segments of RNA can be rewritten into DNA. “The reality that a human polymerase can do this with great efficiency raises many questions.”, says Richard Pomerantz. In particular, this may indicate that RNA messages can be used as templates to repair or rewrite genomic DNA.
Converting RNA to DNA, the main function of polymerase theta?
For this study, the researchers studied a very unusual polymerase, called polymerase theta. Of the 14 DNA polymerases present in our cells, only three do most of the work of duplicating the entire genome to prepare for cell division. The others are mainly involved in the detection and repair in case of breaks or errors in the DNA strands. Polymerase theta is one of these but is particularly error-prone and in particular causes many errors or mutations. Looking closer, the researchers noticed that polymerase theta shares some of its “bad” qualities with reverse transcriptase, an enzyme that is able to convert RNA into DNA, which can be found especially in HIV. . These enzymes are used by retroviruses that contain RNA.
In a series of experiments, the researchers tested polymerase theta versus HIV reverse transcriptase. They showed that polymerase theta is able to convert RNA messages into DNA even more efficiently than during DNA duplication. This discovery suggests that this function could be its main purpose in the cell. To confirm this, the researchers used X-ray crystallography and found that this molecule is able to change shape in order to accommodate the larger RNA molecule, which would be “a unique feat among polymerases”, note the researchers.
Does the question, faced with this discovery, of a possible transmission of the SARS-CoV-2 coronavirus genome in DNA via messenger RNA vaccines arise? An analysis of the mechanism of these vaccines carried out in January 2021 provides the elements of a negative answer. Unlike that of HIV, the genome of the coronavirus does not contain the information that would allow it to enter the nucleus of cells and integrate cellular DNA.
Promote the growth of unhealthy cells
On the other hand, this new function of cells capable of reconverting RNA sequences into DNA could provide new elements in understanding the mechanism of cancer cell growth. “Our research suggests that the primary function of polymerase theta is to act as a reverse transcriptaseconcluded Dr. Pomerantz. In healthy cells, the purpose of this molecule may be DNA repair by RNA. In unhealthy cells, such as cancer cells, polymerase theta is highly expressed and promotes cancer cell growth and drug resistance. It will be exciting to better understand how polymerase theta activity on RNA contributes to DNA repair and cancer cell proliferation..”
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