title: Artificial box C/D RNAs affect pre-mRNA maturation in human cells.
abstract: Box C/D small nucleolar RNAs (snoRNAs) are known to guide the 2'-O-ribose methylation of nucleotides in eukaryotic ribosomal RNAs and small nuclear RNAs. Recently snoRNAs are predicted to regulate posttranscriptional modifications of pre-mRNA. To expand understanding of the role of snoRNAs in control of gene expression, in this study we tested the ability of artificial box C/D RNAs to affect the maturation of target pre-mRNA. We found that transfection of artificial box C/D snoRNA analogues directed to HSPA8 pre-mRNAs into human cells induced suppression of the target mRNA expression in a time- and dose-dependent manner. The artificial box C/D RNA directed to the branch point adenosine of the second intron, as well as the analogue directed to the last nucleotide of the second exon of the HSPA8 pre-mRNA caused the most prominent influence on the level of HSPA8 mRNAs. Neither box D nor the ability to direct 2'-O-methylation of nucleotides in target RNA was essential for the knockdown activity of artificial snoRNAs. Inasmuch as artificial box C/D RNAs decreased viability of transfected human cells, we propose that natural snoRNAs as well as their artificial analogues can influence the maturation of complementary pre-mRNA and can be effective regulators of vital cellular processes.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Lavrentiev Avenue 8, Novosibirsk 630090, Russia. stepanovga@niboch.nsc.ru
authors.forename: Grigoriy A
authors.initials: GA
authors.lastname: Stepanov
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Semenov
authors.forename: Anna V
authors.initials: AV
authors.lastname: Savelyeva
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kuligina
authors.forename: Olga A
authors.initials: OA
authors.lastname: Koval
authors.forename: Igor V
authors.initials: IV
authors.lastname: Rabinov
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Richter
mesh_terms: D001483:Base Sequence; D002470:Cell Survival; D004722:Endoribonucleases / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D050883:HSC70 Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D061986:MCF-7 Cells; D008745:Methylation; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000235:genetics / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000737:chemistry / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012322:RNA Precursors / Q000737:chemistry* / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000737:chemistry* / Q000235:genetics
chemical_list: D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D009711:Nucleotides; D012322:RNA Precursors; D020537:RNA, Small Nucleolar; D009713:Nucleotidyltransferases; C034038:mRNA maturase; D004722:Endoribonucleases