Obad, S., Dos Santos, C. O., Petri, A., Heidenblad, M., Broom, O., Ruse, C., Fu, C., Lindow, M., Stenvang, J., Straarup, E. M., Hansen, H. F., Koch, T., Pappin, D., Hannon, G. J., Kauppinen, S.
(2011)
Silencing of microRNA families by seed-targeting tiny LNAs.
Nature Genetics, 43 (4).
pp. 371-380.
ISSN 10614036 (ISSN)
Abstract
The challenge of understanding the widespread biological roles of animal microRNAs (miRNAs) has prompted the development of genetic and functional genomics technologies for miRNA loss-of-function studies. However, tools for exploring the functions of entire miRNA families are still limited. We developed a method that enables antagonism of miRNA function using seed-targeting 8-mer locked nucleic acid (LNA) oligonucleotides, termed tiny LNAs. Transfection of tiny LNAs into cells resulted in simultaneous inhibition of miRNAs within families sharing the same seed with concomitant upregulation of direct targets. In addition, systemically delivered, unconjugated tiny LNAs showed uptake in many normal tissues and in breast tumors in mice, coinciding with long-term miRNA silencing. Transcriptional and proteomic profiling suggested that tiny LNAs have negligible off-target effects, not significantly altering the output from mRNAs with perfect tiny LNA complementary sites. Considered together, these data support the utility of tiny LNAs in elucidating the functions of miRNA families in vivo. © 2011 Nature America, Inc. All rights reserved.
| Item Type: |
Paper
|
| Uncontrolled Keywords: |
locked nucleic acid
microRNA
oligonucleotide
animal cell
animal tissue
article
breast tumor
controlled study
female
gene silencing
genetic transfection
human
human cell
mouse
nonhuman
priority journal
proteomics
upregulation
3' Untranslated Regions
Animals
Base Sequence
Cell Line, Tumor
Gene Knockdown Techniques
Genes, Reporter
Genetic Techniques
Hela Cells
Humans
Liver
Luciferases, Renilla
Mammary Neoplasms, Experimental
Mice
Mice, Inbred BALB C
MicroRNAs
Oligonucleotides
Animalia
Mus |
| Subjects: |
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA |
| CSHL Authors: |
|
| Communities: |
CSHL Cancer Center Program > Cancer Genetics
CSHL Cancer Center Program > Signal Transduction
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Proteomics Service
CSHL labs > Hannon lab
CSHL Cancer Center Shared Resources > Mass Spectrometry Service |
| Depositing User: |
Matt Covey
|
| Date: |
2011 |
| Date Deposited: |
09 Jan 2013 16:16 |
| Last Modified: |
05 Jan 2017 19:34 |
| PMCID: |
PMC3541685 |
| Related URLs: |
|
| URI: |
https://repository.cshl.edu/id/eprint/26427 |
Actions (login required)
 |
Administrator's edit/view item |
