Artificial Box CD RNAs Affect Pre-mRNA Maturation in Human Cells

Abstract EN

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.