Scientists have discovered a new mechanism of gene regulation

A group of scientists from Russia studied the role of double-stranded fragments of maturing RNA and showed that the interaction between its distant parts can regulate gene expression. The research is published in Nature Communications.

DNA and RNA – deoxyribonucleic and ribonucleic acids – are the most important parts of the human body. DNA is a macromolecule that provides storage, transmission from generation to generation and implementation of the genetic program for the development and functioning of living organisms. A DNA molecule stores biological information in the form of a genetic code, consisting of a sequence of nucleotides. In turn, RNA is one of the three main macromolecules (the other two are DNA and proteins) that are found in the cells of all living organisms and play an important role in coding, reading, regulating and expressing genes.

In school, we learn that DNA is double-stranded and RNA is single-stranded. But it is not so. Scientists were faced with a situation where RNA formed a double-stranded (so-called secondary) structure, which plays an important role in the functioning of its molecules. These structures are involved in the regulation of gene expression, where double-stranded regions usually have specific functions and, if lost, can cause serious disruption. The double-stranded structure is created by sticky additional areas.

The RNA contains the following nucleosides:

  • Adenine + ribose = adenosine (A)
  • Guanine + ribose = guanosine (G)
  • Cytosine + ribose = cytidine (C)
  • Uracil + ribose = uridine (U)

In the case of nucleic acids, both oligo- and polynucleotides, the nitrogenous bases of nucleotides, due to the formation of hydrogen bonds, are capable of forming paired adenine-thymine (or uracil in RNA) and guanine-cytosine complexes during the interaction of nucleic acid chains. This interaction is called complementarity of nucleic acids and it plays a key role in a number of fundamental processes of storage and transmission of genetic information: DNA replication, which ensures the transfer of genetic information during cell division, transcription of DNA into RNA during the synthesis of proteins encoded by the gene DNA, storage of genetic information in double-stranded DNA and the processes of DNA repair when it is damaged.

In other words, for the pieces of RNA to “stick” to each other, the letters U and G must be displayed opposite A and C, respectively. Most of the sticky areas are close together. However, the role of those located at a distance is not entirely clear.

Scientists from the Skoltech Center for Life Sciences, led by Professor Dmitry Pervushin and their colleagues from Russian and international laboratories, conducted a joint study. They used molecular and bioinformatics techniques to analyze the structure and role of complementary RNA regions that are located far from each other but are capable of forming secondary structures.

In general, RNA has two structures – primary and secondary.

The primary structure of nucleic acids is understood as the order, the sequence of the arrangement of mononucleotides in the polynucleotide chain of RNA. This chain is stabilized by 3 ‘, 5’-phosphodiester bonds. In turn, the secondary structure is the conformational arrangement of the main chain of a macromolecule (for example, a polypeptide chain of a protein or a nucleic acid chain), regardless of the conformation of the side chains or relation to other segments. In describing the secondary structure, it is important to determine the hydrogen bonds that stabilize individual fragments of macromolecules.

Thanks to new work, it became clear that the secondary structure plays an important role in the maturation of RNA molecules that carry information, and especially in splicing. This is a process in which the non-coding regions are excised and the coding regions are stitched together (as in the maturation of RNA molecules). Scientists have shown that RNA secondary structures can regulate splicing and thus contribute more to gene regulation than previously thought.

Biologists have published an extensive computational catalog of potentially important RNA structures. However, the authors of the work note that experimental studies in this direction are just beginning.

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Alexandr Ivanov earned his Licentiate Engineer in Systems and Computer Engineering from the Free International University of Moldova. Since 2013, Alexandr has been working as a freelance web programmer.
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