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Registration Number

0212U009040, 0111U005988 , R & D reports

Title

Macromolecules and their complexes in realization of genetic information

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Head

El'skaya Anna Velentynivna, Доктор біологічних наук

Registration Date

27-12-2012

Organization

Institute of Molecular Biology and Genetics of NASU

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With the use of modern methods of computational biology, studies of biologically important molecular systems such as Watson-Crick pair of bases A • T base pair and with hypoxanthine (Hyp). Analyzing the energy dependence of each of the three hydrogen bonds that stabilize the Watson-Crick and Lovdin pairs along IRC, provides that all H-bonds in a pair of bases A • T is a cooperative, mutually reinforcing each other, while H-bond C2H ... O2 paired bases A*•T* behaves anticooperative, be weaker at strengthening the other two. Crystals of yeast eEF1A in complex with fragment nucleotide exchange factor are obtained and analyzed. All these structures have helped in understanding the molecular details of operation EF1A in eubacteria and arhebacteria and helped shed some light on the process of elongation in lower eukaryotes. In particular, there was a difference in the X-ray structures aEF1A and eEF1Ayo eEF1Bab, but it remained unclear whether this difference reflects real differences between arhebacteria and eukaryotes proteins or whether it is the result of differences between the HDF-, GTP conformations and conformation of eEF1A in complex with nucleotide exchange factor. Crystals of eEF1A higher eukaryotes so far are lacking. It is investigated the expression of oncogenic and onkosupresornyh miRNAs. Shown that in renal carcinoma bright cell expression level miR-21 and miR-222 is significantly higher than in the corresponding normal tissues (1.3 - 34 times for miR-21 and 6-19 times for miR-222). Determination of changes in expression of these oncogenic mykroRNK can be used as a biomarker of cancer pathology. We found a significant downregulation of miR-218 in cells of malignant breast tumors compared with corresponding normal tissue samples and correlation between expression onkosupresornoyi miR-218 and GLCE mRNA or the corresponding protein. Thus, inactivation of miR-218 may play a role in the development of breast cancer. Our previous studies have shown protective effect of suppression of the gene encoding 5-lipoxygenase during ischemia-reperfusion myocardium. Also undeniable is the role of miRNAs in the mechanisms of both myocardial damage and cardiac. The observed interaction between 5-lipoxygenase and system maturatsiyi-miRNAs stimulated our research miRNA expression specific to the heart (miRNA-1-and 29th-208th) while suppressing gene 5-lipoxygenase. These data suggest selective suppression effect on 5-lipoxygenase maturatsiyu miRNA: miRNA reduced for-1 increases for miRNA-208th and unchanged for miRNA-29th. Our previous data show the protective effect of silencing of gene encoding 5-lipoxygenase upon ischemia-reperfusion of myocardium. Also the critical role of microRNA for mechanisms of both myocardial injury and cardioprotection. The fact of 5-lipoxygenase interaction with microRNA maturation system stimulated our project for studying of heart-specific microRNAs (miR-1, -29a, and -208a) during lipoxygenase-5 silencing. Obtained data indicate the selective influence of 5-lipoxygenase silencing on microRNA maturation decreasing microRNA-1, increasing microRNA-208a and absence of effect on microRNA-29a.

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Б.С.Негруцький
В.Є.Досенко
В.І.Кашуба, д.б.н.
В.В.Філоненко
Г.В.Єльська
Г.Д.Яремчук
Д.М.Говорун
Л.Г.Горб
М.А.Тукало
П.В.Білан