The mi-RNA Atlas
Scientists have compiled a complete atlas of microRNAs – important regulatory molecules
Phys Tech blog on Naked Science website
microRNAs play an important role in gene regulation and cell differentiation, and they are already almost all known to science. However, little was known about which parts of the genome are involved in the regulation of the microRNAs themselves. The researchers found these sites using a special algorithm, determined the activity of all microRNAs in different tissues, and the results were made publicly available. The scientific work An integrated expression atlas of miRNAs and their promoters in human and mouse is published in the journal Nature Biotechnology.
"microRNAs are one of the most important mechanisms for regulating gene expression. Creating a complete atlas of microRNAs in various cells brings us one step closer to creating a complete picture of gene regulation," comments Yulia Medvedeva, one of the co–authors of the work, senior researcher at the Center for Biotechnology of the Russian Academy of Sciences, lecturer at the Department of Bioinformatics at MIPT.
microRNA is a small RNA molecule about 20 nucleotides long, which is involved in the regulation of genes. In different tissues, the activity of a different set of genes is necessary, and unnecessary genes "jam" microRNA molecules. They are like little policemen: they recognize a gene that should not work in this tissue, and block it. In many diseases, there are deviations in the work of microRNAs, so now antisense microRNA therapy is being developed, for example, for cancer. In addition, microRNA molecules can be used as a medicine, since they can be used to suppress the synthesis of bad proteins. But very little is known about how the microRNA itself is regulated.
The work of microRNAs. If the microRNA "sits down" on the informational RNA, then the synthesis of protein and RNA is blocked.
The RNA links – the nucleotides adenine (A), cytosine (C), guanine (G), uracil (U) – can form C-G, A-U and G-U bonds. For example, CCUA and GGGU sequences will be able to bind and will be called complementary, while CCUA and UCCG will not be complementary. microRNA binds to an almost complementary RNA site and thus prevents protein synthesis from this site.
Precursors of the first open microRNA (top) and the first open microRNA in humans (bottom). Although RNA is a single–stranded molecule, it is not necessarily straight. Thus, the precursors of microRNAs have the shape of a hairpin.
Even 30 years ago, no one knew about microRNAs. It was only in 1993 that the first representative of these non-coding RNAs was described, that is, RNA molecules on the basis of which proteins are not produced. RNA is a single–stranded molecule consisting of links-nucleotides. It is obtained from DNA, a double–stranded molecule in which the RNA sequence is encoded. On the basis of DNA, all RNAs are obtained: both coding (matrix, or informational, RNAs) and non–coding - the translation from DNA to RNA is called "transcription". Informational RNA serves as a "recipe" according to which proteins are produced, and non-coding RNAs participate in the "preparation" of protein. All RNAs must go through several stages of maturation in order to perform their functions. So, special proteins cut out a small piece from an RNA molecule about 80 nucleotides long, and a microRNA is obtained. microRNA is said to be cut from a microRNA precursor, or pre-microRNA.
Transcription begins with the fact that special proteins (transcription factors) sit on the launch pad – a section of DNA next to the gene, which is called a "promoter". microRNA precursors also have promoters, but so far many of them have not been identified accurately enough. For this reason, it has been difficult to study the regulation of microRNAs, although most microRNAs and their precursors are already known. microRNAs are tissue–specific: in some tissues, the precursors of some microRNAs are expressed (translated from DNA to RNA), and in other tissues, others. Due to this, cells in different tissues have different properties (because different sets of genes are blocked).
Interactive expression map. On the top – tissue types, on the right – microRNA, at the intersection – the level of expression of this RNA in this tissue.
Scientists have compiled a complete atlas of microRNAs with promoters of their precursors in different tissues. The work was carried out within the framework of a large research project FANTOM5 (Functional annotation of the mammalian genome – functional characteristics of the mammalian genome), which collects and analyzes data on functional elements in the mouse and human genomes. Previously, they developed a technology (CAGE, Cap Analysis of Gene Expression), with which it is possible to find promoters in the genome. They compared data on promoters with data on short RNAs and identified a precursor and its promoter for each microRNA. Many microRNAs were described earlier, and some new microRNAs were found using a special algorithm. In addition to these data, the atlas contains a map of the expression of the precursors of all microRNAs in more than a hundred types of human tissues. Using this map, you can see in which tissues which microRNAs play their regulatory role.
Vsevolod Makeev, one of the co-authors of the work and professor of the Department of Bioinformatics at MIPT, explains: "When you know where the promoter is located, you can, firstly, try to understand which regulatory cascades this microRNA is included in. And secondly, if a person has mutations in the area where the promoter is located, he may have some kind of regulation violations, and you will know about it, and in the future even, perhaps, correct these violations."
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