Home LiteratureArticle Details
PMID: 20371515 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Numerical modelling of microRNA-mediated mRNA decay identifies novel mechanism of microRNA controlled mRNA downregulation.

Nucleic acids research ·Vol. 38 ·No. 14 ·2010-08-00 ·Pages 4579-85

Vohradsky J, Panek J, Vomastek T

Abstract

Post-transcriptional control of mRNA by micro-RNAs (miRNAs) represents an important mechanism of gene regulation. miRNAs act by binding to the 3' untranslated region (3'UTR) of an mRNA, affecting the stability and translation of the target mRNA. Here, we present a numerical model of miRNA-mediated mRNA downregulation and its application to analysis of temporal microarray data of HepG2 cells transfected with miRNA-124a. Using the model our analysis revealed a novel mechanism of mRNA accumulation control by miRNA, predicting that specific mRNAs are controlled in a digital, switch-like manner. Specifically, the contribution of miRNAs to mRNA degradation is switched from maximum to zero in a very short period of time. Such behaviour suggests a model of control in which mRNA is at a certain moment protected from binding of miRNA and further accumulates with a basal rate. Genes associated with this process were identified and parameters of the model for all miRNA-124a affected mRNAs were computed.

MeSH Terms
Cell Line Down-Regulation Gene Silencing Humans MicroRNAs/metabolism Models, Genetic Oligonucleotide Array Sequence Analysis RNA Stability RNA, Messenger/metabolism
Chemicals
MicroRNAs RNA, Messenger
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Vohradsky Jiri
Institute of Microbiology ASCR vvi, Prague, Czech Republic. vohr@biomed.cas.cz
Panek Josef
Vomastek Tomas
References (37)
37 references, click to expand
  1. RNA-binding protein Dnd1 inhibits microRNA access to target mRNA.
    Cell. 2007 Dec 28;131(7):1273-86 PMID: 18155131
  2. Degradation of microRNAs by a family of exoribonucleases in Arabidopsis.
    Science. 2008 Sep 12;321(5895):1490-2 PMID: 18787168
  3. Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system.
    Genes Dev. 2007 Aug 1;21(15):1857-62 PMID: 17671087
  4. microRNA target predictions in animals.
    Nat Genet. 2006 Jun;38 Suppl:S8-13 PMID: 16736023
  5. Oncomirs - microRNAs with a role in cancer.
    Nat Rev Cancer. 2006 Apr;6(4):259-69 PMID: 16557279
  6. Simulation of prokaryotic genetic circuits.
    Annu Rev Biophys Biomol Struct. 1998;27:199-224 PMID: 9646867
  7. Control of translation and mRNA degradation by miRNAs and siRNAs.
    Genes Dev. 2006 Mar 1;20(5):515-24 PMID: 16510870
  8. Prediction of mammalian microRNA targets.
    Cell. 2003 Dec 26;115(7):787-98 PMID: 14697198
  9. MicroRNA silencing through RISC recruitment of eIF6.
    Nature. 2007 Jun 14;447(7146):823-8 PMID: 17507929
  10. The role of microRNA in the delayed negative feedback regulation of gene expression.
    Biochem Biophys Res Commun. 2007 Jul 6;358(3):722-6 PMID: 17509530
  11. Combinatorial microRNA target predictions.
    Nat Genet. 2005 May;37(5):495-500 PMID: 15806104
  12. microRNAs in vertebrate physiology and human disease.
    Annu Rev Genomics Hum Genet. 2007;8:215-39 PMID: 17506656
  13. Neural network model of gene expression.
    FASEB J. 2001 Mar;15(3):846-54 PMID: 11259403
  14. Repression of protein synthesis by miRNAs: how many mechanisms?
    Trends Cell Biol. 2007 Mar;17(3):118-26 PMID: 17197185
  15. MicroRNA targeting specificity in mammals: determinants beyond seed pairing.
    Mol Cell. 2007 Jul 6;27(1):91-105 PMID: 17612493
  16. Genexp--a genetic network simulation environment.
    Bioinformatics. 2002 Oct;18(10):1400-1 PMID: 12376387
  17. Reconstructing repressor protein levels from expression of gene targets in Escherichia coli.
    Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18592-6 PMID: 17121995
  18. MicroRNAS and their regulatory roles in plants.
    Annu Rev Plant Biol. 2006;57:19-53 PMID: 16669754
  19. Computational modeling of post-transcriptional gene regulation by microRNAs.
    J Comput Biol. 2008 Apr;15(3):305-16 PMID: 18333757
  20. Quantitative characteristics of gene regulation by small RNA.
    PLoS Biol. 2007 Sep;5(9):e229 PMID: 17713988
  21. Target-specific and global effectors in gene regulation by MicroRNA.
    Biophys J. 2007 Dec 1;93(11):L52-4 PMID: 17872959
  22. Regulation of gene expression by small non-coding RNAs: a quantitative view.
    Mol Syst Biol. 2007;3:138 PMID: 17893699
  23. Relief of microRNA-mediated translational repression in human cells subjected to stress.
    Cell. 2006 Jun 16;125(6):1111-24 PMID: 16777601
  24. The let-7 microRNA reduces tumor growth in mouse models of lung cancer.
    Cell Cycle. 2008 Mar 15;7(6):759-64 PMID: 18344688
  25. MicroRNAs: small RNAs with a big role in gene regulation.
    Nat Rev Genet. 2004 Jul;5(7):522-31 PMID: 15211354
  26. Neural model of the genetic network.
    J Biol Chem. 2001 Sep 28;276(39):36168-73 PMID: 11395518
  27. Systematic identification of microRNA functions by combining target prediction and expression profiling.
    Nucleic Acids Res. 2006 Mar 20;34(5):1646-52 PMID: 16549876
  28. Illuminating the silence: understanding the structure and function of small RNAs.
    Nat Rev Mol Cell Biol. 2007 Jan;8(1):23-36 PMID: 17183358
  29. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
    Nat Rev Genet. 2008 Feb;9(2):102-14 PMID: 18197166
  30. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.
    Cell. 2005 Jan 14;120(1):15-20 PMID: 15652477
  31. Role of microRNAs in plant and animal development.
    Science. 2003 Jul 18;301(5631):336-8 PMID: 12869753
  32. The evolution of gene regulation by transcription factors and microRNAs.
    Nat Rev Genet. 2007 Feb;8(2):93-103 PMID: 17230196
  33. Mutations that lead to reiterations in the cell lineages of C. elegans.
    Cell. 1981 Apr;24(1):59-69 PMID: 7237544
  34. Towards a circuit engineering discipline.
    Curr Biol. 2000 Apr 20;10(8):R318-20 PMID: 10801411
  35. Widespread microRNA repression by Myc contributes to tumorigenesis.
    Nat Genet. 2008 Jan;40(1):43-50 PMID: 18066065
  36. MicroRNAs direct rapid deadenylation of mRNA.
    Proc Natl Acad Sci U S A. 2006 Mar 14;103(11):4034-9 PMID: 16495412
  37. It's a noisy business! Genetic regulation at the nanomolar scale.
    Trends Genet. 1999 Feb;15(2):65-9 PMID: 10098409
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkq220
Email
vohr@biomed.cas.cz
Published
2010-08-00
Epub
2010-00-05
Pages
4579-85
Language
English
Region
England
NLM ID
0411011
PMCID
PMC2919720
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkq220 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2