In these months, there has been a lot of talk about mRNA and DNA, especially with the advent of Pfizer’s and Moderna’s vaccines and their new mRNA technology. Immediately, the machine of the “doubters” was set in motion to discredit these ingenious lifesavers: “the mRNA of vaccines modifies our DNA!!” and “they put too many copies of mRNA in it!!” are two of the many phrases heard and on which I want to focus on today.
Thus. we inaugurate the first post of the series “welcome to celltropolis” (find the introduction here), explaining the difference between DNA and mRNA.

DNA: the code of life

Let’s start by defining what DNA is and why it is considered the code of life.
Let’s dive ourselves in our metropolis: as mentioned in the introductory post, inside the cell there is a structure surrounded by walls (the nucleus). We can consider this structure as a large library, whose access is monitored and inside which many androids and machinery work to make life in the metropolis possible. In fact, in this library 23 pairs of books of different sizes (the chromosomes) are kept, studied and read constantly, divided into 22 pairs of autosomal books and a pair of sexual books (XX in the case of females, XY in the case of of males).
We speak of “couples” becaus, at the moment of conception, a copy is inherited from the mother and a copy from the father for each of the 23 books; the two copies, under normal conditions, contain the same information, even if they are written differently (you will understand better what I mean soon).

However, you must not imagine these couples as one; in fact, they are scattered throughout the library and come into “contact” only in a particular phase of life, called meiosis, of specific cells (this topic will be addressed in a future post).
To make you understand how big these books are, all together they contain 6,200,000,000 characters (on even pages, and as many on odd pages) ¹; the smallest book (chromosome 21) contains about 48,000,000 ² while Tolstoy’s “war and peace” contains about 3,200,000 ³; this means that our “smallest” book is as long as almost 15 tomes of “war and peace” one after the other.


You may be wondering what is written in these books, and here is the answer: these books contain instructions to ensure that everything works within the metropolis. There are directions to build buildings, roads, androids, machinery, factories, to create new cities, etc.
But you have to imagine these instructions a bit like the old IKEA instructions: incomprehensible to most. In fact, each of these books contains a very long sequence consisting of only 4 characters (the nucleobases): A, C, G and T. A peculiarity of these books is that the pages are written in a peculiar way. Imagine having even pages on the left side (starting from 0) and odd pages on the right side; each odd page is the copy of the even page, with a big difference: to each A of the even page, there is a T in the odd one, to each C a G, to each G a C and to each T an A.

In the figure, you can see an example of this concept: on page 6 the initial sequence of characters is ACTGCTATAGC, while on page 7 the sequence is TGACGATATCG.
Another feature of these books is that even pages must be read from left to right, from top to bottom; while the odd pages should be read from right to left, from bottom to top.
In addition, as previously mentioned, the two copies are not at all the same; on the contrary, they are often very different in terms of code, but we will see in a future article how these differences, under “normal” conditions, do not cause any problem.


After having talked about the code, let’s see how this is used. As in any metropolis, the production of goods and resources is highly regulated: there are resources that must be always produced (cables, pipes, bricks, working androids, latches, patrols, …), others that must be produced when required (for example army-androids specialized in the event of an “external attack”, other factories when there is a need to increase the general production of goods) and others whose production must be temporarily blocked (for example general production in case of drought/famine).
Since the production instructions are contained in the library books, someone needs to bring them to the factories. There is a little problem: books can never leave the library (except when the cell is dividing), and, above all, factories are unable to read the code as it is in books; for this reason, there is a need for someone to rewrite the directions in a language that is understandable to factories. This process is called transcription and it is carried out by a complex machine called RNA polymerase: without going into details, this machine (similar to a photocopier) copies the pages relating to a specific resource and creates a booklet that will then be useful to factories. This booklet is called messenger RNA (mRNA).

mRNA: the metropolis messengers

Let’s see the characteristics of the mRNA and why it is so different from DNA. In the first place, to ensure that it can be read and understood by factories, the code is different: the copier recreates the page opposite to the one it scans and putting the U in place of the T. Taking the example of the previous figure, if the copier were to read page 6, what would come out would be the sequence UGACGAUAUCG. Written this way, factories are able to understand it and create what they are told.
Secondly, this booklet must come out of the library and arrive at the factory. To ensure that this booklet is recognized by the guards at the library exits and allowed to go out, it is given a special cover called 5 ‘cap. This cover provides the booklet with a one way ticket out of the library; once out, no booklets will be allowed to re-enter the library.
Another function of the cap is to protect the booklet (just like a hard cover) during the journey to the factories. Unfortunately the cover alone is not enough to protect the booklet as it is only on the front page; to protect the code of the last pages, after reading the original book, the copier adds about 200 A at the end of the sequence, so that if you were to ruin a few pages at the bottom, only the A’s would be ruined and not the code part fundamental for factories.

But why should the booklet be protected?
A legitimate question, and here is the answer: since these booklets carry instructions on what to produce, viruses and bacteria use their own booklets to make the cell produce their proteins (their “resources”) and to reproduce; to protect us, there are patrols that go around the metropolis in search of booklets and, once found, destroy them. In most cases, the virus and bacteria booklets do not have the protections that ours have, and therefore they are destroyed more easily.

Mythbuster

We come to the crucial points of the post, busting the two myths mentioned in the introduction of this post (plus an extra one).

“The mRNA of vaccines modifies our DNA !!"
Since mRNAs cannot enter the nucleus (remember the one-way ticket and the guards at the library doors seen earlier?), the vaccine ones entering from outside are unable to get inside the library and modify the DNA. And to those who claim that mRNA is converted to DNA (as if there were reverse copiers scattered around the metropolis), you should answer that this could (in rare cases) only happen in cells infected by some retrovirus (such as HIV) and that therefore the conversion from mRNA to DNA is the least of the problems for that person.

“They put too many copies of mRNA in it !!"
Usually, a cell contains between 10 and 30 µg of mRNA⁴ (1µg equals 0.000000000001g). The vaccine contains 30 μg of mRNA⁵, equivalent to the content of 1,000,000 cells; but there is no need to be frightened, as in our body there are many many many more cells, and the vaccine is not absorbed by one or a few cells, but by millions of them. To give you an idea of how small the cells are and how insignificant that number is, if you take a 3cm-diameter plastic disc and grow cells to form a single (one!) layer, you can have up to 1.5 million cells.

“The mRNA stays for life then!"
This statement is also incorrect. Although mRNAs are protected (as we have seen before), their average life span varies between a few minutes and a few hours ⁶; they too are subject to constant turnover.

Now you too are ready to bust these myths.