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Messenger RNA, this new hero

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Published the 12/3/2020

A cell is like a big factory that is always in turmoil. When we zoom in on the part of a cell called the nucleus, we find our genetic makeup in the form of chromosomes. These are our DNA, coiled up and as condensed as possible, so that it doesn't take up too much space. Because not condensed, it would measure about 2 meters.



This DNA contains what are called genes, the information to synthesize proteins (See the article "The protein, that unknown star"). During this protein synthesis, two major steps take place: transcription and translation. Here, only the translation will interest us, because it is during this that we find the messenger RNA. The same messenger RNA that, with the emergence of vaccines using it against Covid-19, is in the spotlight.

Understanding what messenger RNA is

What is messenger RNA and what is it used for? To answer it, we have to dive back into the nucleus of our cell by positioning ourselves at the level of DNA, that is to say two long strands which complement each other like the pieces of a puzzle via what is called nucleotides. These go in pairs, C (cytosine) with G (guanine) and A (adenine) with T (thymine).

These two so-called complementary strands are wound on themselves. A very heavy worker in the enzyme category then kicks in, RNA polymerase II. It will split our DNA in half and at the same time produce a molecule that looks like DNA from a distance but is actually messenger RNA.




Diagram of the synthesis of messenger RNA by RNA polymerase II

Messenger RNA is a single-stranded molecule (unlike DNA which has two), which is called transient because it only passes through our cells. Its role is to allow the production of proteins.


Messenger RNA and Covid-19, an intimate relationship

Covid-19 is a coronavirus. Once inside our body, this goes to our cells to inject its RNA (not DNA) and reproduce there. This is why, when testing for the virus we talk about RT-PCR tests, (RT for Reverse Transcriptase and not just PCR, for Polymerase Chain Reaction). RT-PCR is used for RNA, while PCR is for DNA. This test is the most commonly used and is used to determine the amount of virus messenger RNA in our body.

How is the quantity of messenger RNA measured during this RT-PCR? For this, the famous samples in the nose are carried out. Two techniques follow: one where the laboratories will first extract the RNA from the sample and the other which will be directly studied without extraction.

For this RT-PCR test, we use a machine called thermocycler where we introduce different elements: a piece of RNA (fragment), two small strands to identify the ends of our piece of RNA (primers), an enzyme allowing to "make DNA from RNA (reverse transcriptase) and some energy (dNTP)." We will then obtain the DNA that would have given the RNA studied. Because yes, let's remember that RNA comes from the transcription of DNA. Here we are going backwards.

From there, a "simple" PCR takes place. We "break" (denature) our DNA and add "pieces" to its ends to identify them (much like identity cards). There follows a first cycle of "DNA cloning" during which our two strands of DNA, until then separated, will be synthesized as a new pair. We then switch from one double strand of DNA to two double stranded DNA. The more cycles are linked, the more the number of double DNA strands will increase. At the end of the 2nd cycle we will have 4, at the 3rd 8 ...

PCR diagram

So we can easily tell ourselves that the more cycles there are, the more DNA we have and therefore the more sensitive the test. But the role of messenger RNA in this Covid-19 story does not end there.


An expanding field of action

In fact, there is a lot of talk about the various vaccines being validated to counter the virus. According to the CNRS journal, 180 vaccines are under development, 40 of which are in the clinical phase in humans, including the RNA vaccine from the Pfizer laboratory. It should be understood that when a foreign RNA enters our body, it is immediately broken down by our enzymes. When we produce a vaccine (see the article "Vaccination, our bodyguard" by Anne Clerico), we try to prepare our body as well as possible to defend itself against the potential aggressor. Several approaches and techniques are then used to construct a vaccine to be effective. Clearly, it must not be destroyed as soon as it arrives in our body. This is why the majority of vaccines in development against Covid-19 have opted for an encapsulated RNA / DNA vaccine (with a protective frame). It is an adaptable vaccine in design and reporting to our immunity soldiers as a foreign body.


Because RNA is necessary for the production of proteins, it does not fit into our genes. Present in our cells but over a short period, it will be quickly eliminated naturally once its role has been fulfilled. It is therefore considered a safe means in terms of vaccination. In addition, this type of vaccine strongly sets in motion our first defenses of the immune system (innate reaction) subsequently allowing a better preparation of our body to fight against the virus. Messenger RNA is therefore a passive element of information that makes the transition between our DNA and proteins. However, messenger RNAs are only a very small part of this large family of RNAs in our cells. These perform various functions such as activating or deactivating our genes, serving as a taxi for other molecules and participating in chemical reactions ... Currently we are experiencing a full expansion of research for these molecules which are RNA in different methods of therapy because they can be anything other than this state of transition between DNA and protein. For our messenger RNA, other than the Covid-19 vaccine, other applications exist: the development of personalized anti-cancer vaccines or against infectious diseases such as the Zika virus ... This small molecule which for a very long time has gone unnoticed until now has therefore not finished showing us its scope.


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