Gene silencing using micro-RNA designed hairpins - PubMed (original) (raw)
Gene silencing using micro-RNA designed hairpins
Michael T McManus et al. RNA. 2002 Jun.
Abstract
During RNA interference (RNAi), long dsRNA is processed to approximately 21 nt duplexes, short interfering RNAs (siRNAs), which silence genes through a mRNA degradation pathway. Small temporal RNAs (stRNAs) and micro-RNAs (miRNAs) are approximately 21 nt RNAs that are processed from endogenously encoded hairpin-structured precursors, and function to silence genes via translational repression. Here we report that synthetic hairpin RNAs that mimic siRNAs and miRNA precursor molecules can target a gene for silencing, and the mechanism of silencing appears to be through mRNA degradation and not translational repression. The sequence and structural configuration of these RNAs are important, and even slight modification in structure can affect the silencing activity of the hairpins. Furthermore, these RNAs are active when expressed by DNA vectors containing polymerase III promoters, opening the possibility for new approaches in stable RNAi-based loss of function studies.
Similar articles
- Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing.
Harborth J, Elbashir SM, Vandenburgh K, Manninga H, Scaringe SA, Weber K, Tuschl T. Harborth J, et al. Antisense Nucleic Acid Drug Dev. 2003 Apr;13(2):83-105. doi: 10.1089/108729003321629638. Antisense Nucleic Acid Drug Dev. 2003. PMID: 12804036 - Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells.
Paddison PJ, Caudy AA, Bernstein E, Hannon GJ, Conklin DS. Paddison PJ, et al. Genes Dev. 2002 Apr 15;16(8):948-58. doi: 10.1101/gad.981002. Genes Dev. 2002. PMID: 11959843 Free PMC article. - Knock-down of gene expression in hematopoietic cells.
Scherr M, Venturini L, Eder M. Scherr M, et al. Methods Mol Biol. 2009;506:207-19. doi: 10.1007/978-1-59745-409-4_15. Methods Mol Biol. 2009. PMID: 19110629 - Post-transcriptional gene silencing by siRNAs and miRNAs.
Filipowicz W, Jaskiewicz L, Kolb FA, Pillai RS. Filipowicz W, et al. Curr Opin Struct Biol. 2005 Jun;15(3):331-41. doi: 10.1016/j.sbi.2005.05.006. Curr Opin Struct Biol. 2005. PMID: 15925505 Review. - RNA interference: the molecular immune system.
Bagasra O, Prilliman KR. Bagasra O, et al. J Mol Histol. 2004 Aug;35(6):545-53. doi: 10.1007/s10735-004-2192-8. J Mol Histol. 2004. PMID: 15614608 Review.
Cited by
- Functional VEGFA knockdown with artificial 3'-tailed mirtrons defined by 5' splice site and branch point.
Kock KH, Kong KW, Hoon S, Seow Y. Kock KH, et al. Nucleic Acids Res. 2015 Jul 27;43(13):6568-78. doi: 10.1093/nar/gkv617. Epub 2015 Jun 18. Nucleic Acids Res. 2015. PMID: 26089392 Free PMC article. - Enhanced gene silencing of HIV-1 specific siRNA using microRNA designed hairpins.
Boden D, Pusch O, Silbermann R, Lee F, Tucker L, Ramratnam B. Boden D, et al. Nucleic Acids Res. 2004 Feb 13;32(3):1154-8. doi: 10.1093/nar/gkh278. Print 2004. Nucleic Acids Res. 2004. PMID: 14966264 Free PMC article. - Gene silencing of EXTL2 and EXTL3 as a substrate deprivation therapy for heparan sulphate storing mucopolysaccharidoses.
Kaidonis X, Liaw WC, Roberts AD, Ly M, Anson D, Byers S. Kaidonis X, et al. Eur J Hum Genet. 2010 Feb;18(2):194-9. doi: 10.1038/ejhg.2009.143. Epub 2009 Aug 19. Eur J Hum Genet. 2010. PMID: 19690583 Free PMC article. - Akt regulates basic helix-loop-helix transcription factor-coactivator complex formation and activity during neuronal differentiation.
Vojtek AB, Taylor J, DeRuiter SL, Yu JY, Figueroa C, Kwok RP, Turner DL. Vojtek AB, et al. Mol Cell Biol. 2003 Jul;23(13):4417-27. doi: 10.1128/MCB.23.13.4417-4427.2003. Mol Cell Biol. 2003. PMID: 12808085 Free PMC article. - Native microRNA loop sequences can improve short hairpin RNA processing for virus gene silencing in animal cells.
Hinton TM, Wise TG, Cottee PA, Doran TJ. Hinton TM, et al. J RNAi Gene Silencing. 2008 May 27;4(1):295-301. J RNAi Gene Silencing. 2008. PMID: 19771239 Free PMC article.
References
- Nat Cell Biol. 2000 Feb;2(2):70-5 - PubMed
- Nat Genet. 2000 Feb;24(2):180-3 - PubMed
- Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3142-7 - PubMed
- Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4985-90 - PubMed
- Nat Biotechnol. 2000 Aug;18(8):896-8 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials