ИСТИНА

Different external and internal stimuli require the rapid and appropriate response from the cells. Posttranslational modifications control the localization, stability and activity of proteins that allow transfer the accepted signals to the biological outcomes. PAPR1 or poly(ADP-ribose) polymerase 1 is able to catalyze the reaction of covalent synthesis of long branched chains of poly(ADP-ribose) utilizing NAD+ as a substrate. PARP1 is widely known as the key regulator of systems of cellular DNA damage response and systems of programmed cellular death, but its functions not only restricted with these systems. PAPR1 has a lot of other functions, such as global regulation of transcription, telomere maintaining and involvement in development of inflammation. PARylation regulates the protein-protein and protein-nucleic acids interactions. The attachment of large negatively charged ADP-ribose to the protein modulates the activity and interactome of targeted protein. The influence of PARylation on the protein-DNA complexes is well-studied. It is known the impairment of PARylation in the chromatin remodeling by ISWI, nucleosome-nucleosome interactions involved in the regulation of chromatin condensation, telomere binding by TRF1 and many other. Recently, it was shown the involvement of PARP1 in RNA biogenesis. It was demonstrated the PARylation of the H/ACA-proteins that involved in the ribosome biogenesis and pre-mRNA splicing, as well as in assembly and stability of human telomerase complex. H/ACA ribonucleoprotein complex contains four proteins: DKC1, GAR1, NHP2 and NOP10, two of which (DKC1 and GAR1) were identified as targets of PARP1. We proposed that post-translational modification of RNA-binding protein should regulate the complex assembly and stability implementing the modulation of its activity. We demonstrated that PARylation of DKC1 and GAR1 influences on the pattern of RNA associated with the targeted proteins. The additional analysis of telomerase complex assembly, stability and activity revealed that PARylation decreases the telomerase complex stability resulting in the inhibition of telomerase activity. This work was supported by the Russian Foundation for Basic Research [18-29-07031 mk], Russian Science Foundation [19-14-00065], and Lomonosov Moscow State University Development Program [PNR 5.13].