Analogues of Artificial Human Box C/D Small Nucleolar RNA As Regulators of Alternative Splicing of a pre-mRNA Target

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Abstract


Small nucleolar RNAs (snoRNAs) play a key role in ribosomal RNA (rRNA) biogenesis. Box C/D snoRNAs guide the site-specific 2’-O-ribose methylation of nucleotides in rRNAs and small nuclear RNAs (snRNAs). A number of box C/D snoRNAs and their fragments have recently been reported to regulate post-transcriptional modifications and the alternative splicing of pre-mRNA. Artificial analogues of U24 snoRNAs directed to nucleotides in 28S and 18S rRNAs, as well as pre-mRNAs and mature mRNAs of human heat shock cognate protein (hsc70), were designed and synthesized in this study. It was found that after the transfection of MCF-7 human cells with artificial box C/D RNAs in complex with lipofectamine, snoRNA analogues penetrated into cells and accumulated in the cytoplasm and nucleus. It was demonstrated that the transfection of cultured human cells with artificial box C/D snoRNA targeted to pre-mRNAs induce partial splicing impairments. It was found that transfection with artificial snoRNAs directed to 18S and 28S rRNA nucleotides, significant for ribosome functioning, induce a decrease in MCF-7 cell viability.


G. A. Stepanov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Author for correspondence.
Email: stepanovga@niboch.nsc.ru

Russian Federation

D. V. Semenov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: stepanovga@niboch.nsc.ru

Russian Federation

E. V. Kuligina

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: stepanovga@niboch.nsc.ru

Russian Federation

O. A. Koval

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: stepanovga@niboch.nsc.ru

Russian Federation

I. V. Rabinov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: stepanovga@niboch.nsc.ru

Russian Federation

Yu. Ya. Kit

Institute of Cell Biology, National Academy of Sciences of Ukraine

Email: stepanovga@niboch.nsc.ru

Ukraine

V. A. Richter

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences

Email: stepanovga@niboch.nsc.ru

Russian Federation

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Copyright (c) 2012 Stepanov G.A., Semenov D.V., Kuligina E.V., Koval O.A., Rabinov I.V., Kit Y.Y., Richter V.A.

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