"Handles from the frying pan"
Biologists have discovered a new mechanism for controlling the activity of genes
Scientists from Russia and Spain have found out that loops and other complex spatial structures that periodically arise inside RNA molecules in living cells can play an important role in controlling gene activity. The results of the study were published in the scientific journal Nature Communications (Kalmykova et al., Conserved long-range base pairs are associated with pre-mRNA processing of human genes).
For a long time, biologists assumed that the level of activity of a gene depends solely on its structure. In the last century, scientists found out that this is not the case. It turned out that many other factors influence the work of genes, including how DNA is "packed" inside the cell nucleus, how selectively cellular mechanisms read the part of the genome where a particular gene is located, and which short strands of RNA can interact with its "working" copies, matrix RNA molecules.
Due to the fact that there are many similar mechanisms, the human body and other living beings can very flexibly regulate the activity level of most genes, adapting to changing environmental conditions. Due to disturbances in the work of this process, which biologists call gene expression, cancer and other serious diseases can occur.
Studying what role double rather than single RNA chains play in the vital activity of the organism, which are usually the main focus of research, Professor Dmitry Pervushin of the Skolkovo Institute of Science and Technology and his colleagues discovered another mechanism that controls the activity of genes.
Double strands of RNA arise inside long strands of RNA as a result of interactions between their individual segments and single "letters"-nucleotides. As a result, loops, rings and other complex spatial structures are formed, which scientists call "frying pan handles". They significantly change the properties of the entire RNA chain, but the exact mechanisms of their work remained unexplored.
Having identified several dozen "handles from the frying pan", the researchers calculated in detail how their appearance would affect the expression of genes in general. It turned out that such structures play an important role in the process of splicing – the primary processing of a matrix RNA molecule after its assembly. During this process, the cell removes unnecessary parts of the chain and stitches its fragments together.
In particular, in the vicinity of those parts of the RNA strand that the cell actively removes during splicing, they were unusually rare and almost did not occur inside those segments of it that the cell cuts out during this process. In addition, they influenced how actively RNA molecules interacted with certain types of proteins that modify the structure of their strands, and also influenced the work of genes in other ways.
Guided by similar considerations, Russian and Spanish biologists have identified several genes – RALGAPA1, FGFR1OP2 and others, whose work can be strongly influenced by variations in the structure of RNA. They hope that further research will help to find out the role of "frying pan handles" in the appearance of malfunctions in the work of these genes and the development of related diseases.
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