Laboratory of regulatory transcriptomics

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Tatyana Azhikina

A new class of antisense oligonucleotides – phosphoryl guanidine oligo-2′-O-methylribonucleotides - specifically inhibits target genes expression in intracellular Mycobacteria

Phosphoryl guanidine oligo-2′-O-methylribonucleotides (2′-OMe PGOs) are a novel type of uncharged RNA analogues. We demonstrated that antisense 2′-OMe PGO inhibits the growth of Mycobacterium smegmatis and downregulates target gene expression at both transcriptional and translational levels. 2′-OMe PGO penetrates into intracellular mycobacteria residing in macrophages without exerting toxic effects on eukaryotic cells, and inhibits the transcription of the target gene in M. smegmatis-infected macrophages. So, these novel oligonucleotide derivatives have a potential as antisense therapeutic agents against tuberculosis, especially its drug-resistant forms

PIWIL2 functions in testicular germ cell tumors development

PIWILs, highly evolutionary conserved proteins, are involved in many cellular processes including carcinogenesis. They function in combination with short non-coding RNAs (piRNAs), determining genomes stability, preventing expression and transposition of mobile elements. We studied functions of the PIWI/piRNA system in germ testicular cells, as well as in testicular germ cell tumors development, and showed predominant expression of short 60 kDa PIWIL2 isoform. Herewith, there is no piRNA biogenesis in tumor cells, and the short PIWIL2 isoform suppresses the expression of young LINE and SINE transposon families post-transcriptionally, which can provide advantages for tumor growth by maintaining the stability of its genome.