24 April 2017

"Junk" DNA helps turn on genes

The activity of a gene is affected by meaningless DNA fragments located inside the gene itself

Kirill Stasevich, "Science and Life"

When we talk about the genome, we imagine a text in which each gene is like one word. Such a comparison is very convenient and to some extent correct: after all, genes in DNA really look like an alternation of four chemical "letters" – the nitrogenous bases of adenine (A), thymine (T), guanine (G) and cytosine (C).

The meaning of genetic "words" manifests itself when the information contained in them turns into a protein: first, an RNA copy comes off the gene, which is then read by protein-synthesizing machines that assemble the protein molecule exactly according to what is written in RNA (RNA synthesis is called transcription, protein synthesis is translation).

However, there are two things worth remembering here. Firstly, genetic "words with meaning" are interspersed with pieces of some nonsense - there are DNA sequences between the genes that do not encode any proteins. Secondly, the "words"-genes themselves consist of fragments called introns and exons.

A gene with two exons and an intron between them (illustration: Wikipedia)

Exons are "semantic" fragments, but there is no information for protein synthesis in introns. Let's imagine the word "cow", in which there is some kind of meaningless sequence of letters (intron) between the syllable "ko-" (one exon) and the remaining part of "-rova" (the second exon), and in order to read "cow", we need to throw out this nonsense. Something similar happens at the molecular level: when an RNA copy of a gene is synthesized in DNA, it initially includes everything as it is, both introns and exons. But then the RNA goes through a procedure called splicing: special enzymes cut out introns and connect exons into a meaningful word.

Both non-coding DNA between genes and introns were once called junk DNA. Various hypotheses have been put forward about how and why it appeared in the course of evolution at all, especially in such numbers (introns, for example, make up 90% of gene sequences in total). But recently there is more and more data, because of which the word "garbage" should be taken in quotation marks. It turns out that such DNA can influence the activity of genes: there are regulatory regions in it that suppress or stimulate the synthesis of RNA copies on "meaningful" DNA sites, while in "junk" DNA, various regulatory RNAs are often encoded - they do not carry protein information, but again serve as a powerful tool for regulating genetic activity.

As for the intronic "garbage", over time it was discovered that if these useless sequences were completely removed from the gene, the gene would become inactive. Introns can be compared to volume controls: let the gene formally work, but it depends on introns how intensively transcription will go on it, how many copies of RNA will be made on the gene.

However, as the experiments of researchers from the University of California at Davis have shown, introns can play the role of not only volume controls, but also genetic switches. In general, special sequences in DNA called promoters serve as switches for genes: they are located in front of the gene and "lure" proteins that are engaged in the synthesis of RNA copies. The promoter is a mandatory regulatory sequence, without it, if the gene will work, it will be very, very bad. But in some cases, as it turned out, introns can take over the function of the switch-promoter.

Jenna Gallegos and Alan Rose experimented with Arabidopsis thaliana plants. They attached a gene to one of the arabidopsis genes that gave a blue pigment: if the plant's own gene worked fine, then an additional "blue" gene worked with it, so that arabidopsis turned blue. When the introns were removed from the gene, then, as expected, it stopped working, and the blue shade of the plant did not appear.

Jenna Gallegos/UC Davis: Plant Genes May Lack Off Switch, But Have Volume Control

But then the promoter was removed from the gene, and the introns, on the contrary, were left where they were. And arabidopsis turned blue. That is, a gene devoid of a switch sequence still worked – thanks to the presence of introns. The authors of the work themselves compare this to the fact that if a radio pulled out of the socket, it still worked when the volume knob was turned to it.

The results of the experiment are described in detail in the article in The Plant Cell (Gallegos, Rose, Intron DNA Sequences Can Be More Important Than the Proximal Promoter in Determining the Site of Transcript Initiation). Now the researchers are faced with the task of deciphering the molecular mechanism of what is happening (that is, how the introns that are inside the gene affect the enzymes that interact with the beginning of the gene), and at the same time find out which genes also have an intron switch, and which lack only a promoter. Perhaps with the help of such switches it will be possible to improve the methods of genetic engineering, making them more efficient and cheaper. 

Portal "Eternal youth" http://vechnayamolodost.ru  24.04.2017

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