The fairy tale of lazy DNA and super-diligent RNA

Prof. Reinhard Renneberg talks about two close and very famous "siblings": one guards the genetic material, the other is a speedy messenger.

DNA and RNA: information guardian and nimble messenger

Good old DNA is important, but not the most industrious. It is a couch potato, stays cosy and - round the clock - guarded at home, in the cell nucleus. The pores of the nucleus are windows, but the immobile DNA doesn't fit through them. And there are no big doors for it - enemies could get in from outside. As I said, the DNA is somewhat frail, does not venture outside into the nevertheless rough world of the cell plasma. Its job is to guard its valuable information from the old days. Occasionally, however, their information is duplicated. This is what we humans call cell and nucleus division (mitosis). 

The small mobile RNA, on the other hand, meanders as a nimble messenger (messenger RNA, mRNA) millions of times over with transcripts of the valuable DNA information from the nucleus. These nimble messengers fit through the pores of the nucleus, straight into the dangerous cell plasma. This is the case in the higher cells of eukaryotes.

"Worker RNAs" are actively ploughing away in the protein factories

In the lower prokaryotes (such as bacteria), on the other hand, the DNA floats "daringly", unprotected, as a giant ring freely in the cell plasma. Here it has dozens of offshoots in the form of small ring-shaped DNA plasmids. These DNA plasmids are mobile (in contrast to the main DNA) and can be exchanged between bacterial cells via so-called sex pili (conjugation). So bacteria also have, well... sex.

In the process, information on the construction of antibiotic-destroying enzymes (lactamases), for example, can be passed on and make their carrier bacteria resistant to antibiotics (much to our chagrin). A real challenge! The RNA siblings, metaphorically speaking, go outside into the wide world instead of sitting at home and just taking care of their heritage. These "worker RNAs" are actively ploughing away in the protein factories, the ribosomes. Their products are then thousands of different proteins of the cell.

Role of RNA only elucidated by two Nobel Prize winners

The important role of RNA was first clearly elucidated by Sidney Altman and Thomas Cech for Ribozymes (Nobel Prize 1989) and further by Jack Szostak (Nobel Prize 2009). Szostak was then the teacher of Jennifer Doudna, who with my good friend Emmanuelle Charpentier won the Nobel Prize in Chemistry for CRISPR. Incidentally, the CRISPR gene scissors rely entirely on active RNA!

Now, however, the medical columnist (true to Brecht's "In Praise of Doubt") wonders what other unplanned surprises the apparently highly active, aggressive RNA in the highly praised mRNA vaccine of a German company (apart from the rather unhealthy flooding of the body with antigenic spike proteins) has up its sleeve... Sic transit gloria mundi (Thus passes the glory of the world) is how my blessed Latin teacher Dr. Friedrich Hohmuth used to describe it in Merseburg, Germany.

What should we know about DNA and RNA?

The linchpin of the bio-revolution is the helix of life - the material carrier of hereditary substance, deoxyribonucleic acid (DNA), internationally abbreviated to DNA. The long search for the carrier of heredity culminated in 1953 in an article in the scientific journal Nature by the two young researchers James Dewey Watson (born 1928) and Francis Compton Crick (1916-2004). In it was a simple but ingenious diagram of a double helix, the DNA double helix.

In simplified terms, DNA can be compared to a twisted zip - a zip, however, that has four different types of "teeth": the four bases adenine (A), cytosine (C), guanine (G) and thymine (T). These bases are part of the nucleotides, the actual building blocks of DNA. The nucleotides, for their part, consist of a sugar, a base and a phosphate residue.

Geometry of the double helix allows access to information from all directions

The geometry of the double helix not only saves space, but also allows access to information from all directions. Deoxyribose is the sugar of the nucleotides. Unlike ribose - the sugar of ribonucleic acid, RNA - deoxyribose lacks the oxygen atom on the 2'-carbon. The backbone consists of alternating deoxyribose and phosphate units. The sugars are thus connected to each other via phosphodiester bridges.

Like zip teeth on a strip of fabric, the four bases are attached to the backbone, which only has a load-bearing function. For the genetic information, only the order of the four bases is important, the base sequence. The two ridges of teeth of a closed zip are mechanically held together.

Watson-Crick rule as a prerequisite for the exact transfer of genetic information

In the case of the two DNA strands, on the other hand, it is molecular interactions, hydrogen bonds (H-bridges), that act between opposite bases of the two individual strands. In 1950, Erwin Chargaff (1905-2002) had determined with the help of chromatographic methods that the ratio of adenine to thymine and of guanine to cytosine is always about 1 in all living organisms (Chargaff's rule).

From Watson and Crick's DNA model it now became clear why this must be so: A-bases and T-bases as well as C-bases and G-bases fit together spatially exactly: Three hydrogen bonds hold G and C together, two H-bridges A and T. This so-called base pairing rule (or Watson-Crick rule) is a prerequisite for the exact transmission of genetic information.

mRNA bridges the gap between nucleus and factory

The genomic DNA of prokaryotic bacteria floats freely in the plasma, while the eukaryotic DNA is tightly entangled in the cell nucleus. In addition to the genomic DNA in the cell nucleus, eukaryotes also possess mitochondrial DNA and plant cells additionally possess DNA in their chloroplasts. Proteins are produced outside the nucleus in the cell plasma. The cell has its own protein factories there, the ribosomes.

This gap between the nucleus and the factory must be bridged. How does the building instruction contained in the DNA in the cell nucleus get to the ribosomes in the cell plasma? A messenger is needed. Such a biological messenger is also necessary for "cell-economic" reasons. The mRNA!

  1. (In German): Reinhard Renneberg: Biotechnologie für Einsteiger