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Human box C/D snoRNAs with miRNA like functions : expanding the range of regulatory RNAs

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50488

Reinhardt,  Richard
High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zitation

Brameier, M., Herwig, A., Reinhardt, R., Walter, L., & Gruber, J. (2011). Human box C/D snoRNAs with miRNA like functions: expanding the range of regulatory RNAs. Nucleic Acids Research, 39(2), 675-686. doi:10.1093/nar/gkq776.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-77E2-9
Zusammenfassung
Small nucleolar RNAs (snoRNAs) and microRNAs are two classes of non-protein-coding RNAs with distinct functions in RNA modification or post-transcriptional gene silencing. In this study, we introduce novel insights to RNA-induced gene activity adjustments in human cells by identifying numerous snoRNA-derived molecules with miRNA-like function, including H/ACA box snoRNAs and C/D box snoRNAs. In particular, we demonstrate that several C/D box snoRNAs give rise to gene regulatory RNAs, named sno-miRNAs here. Our data are complementing the increasing number of studies in the field of small RNAs with regulatory functions. In massively deep sequencing of small RNA fractions we identified high copy numbers of sub-sequences from >30 snoRNAs with lengths of ≥18 nt. RNA secondary structure prediction indicated for a majority of candidates a location in predicted stem regions. Experimental analysis revealed efficient gene silencing for 11 box C/D sno-miRNAs, indicating cytoplasmic processing and recruitment to the RNA silencing machinery. Assays in four different human cell lines indicated variations in both the snoRNA levels and their processing to active sno-miRNAs. In addition we show that box D elements are predominantly flanking at least one of the sno-miRNA strands, while the box C element locates within the sequence of the sno-miRNA guide strand.