Skip Navigation

Nucleic Acids Research 2004 32(21):6284-6291; doi:10.1093/nar/gkh968
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (624K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (50)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Kloosterman, W. P.
Right arrow Articles by Plasterk, R. H.A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kloosterman, W. P.
Right arrow Articles by Plasterk, R. H.A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published online 7 December 2004

Nucleic Acids Research, Vol. 32 No. 21 © Oxford University Press 2004; all rights reserved

Substrate requirements for let-7 function in the developing zebrafish embryo

Wigard P. Kloosterman, Erno Wienholds, René F. Ketting and Ronald H.A. Plasterk*

The Hubrecht Laboratory, Centre for Biomedical Genetics, 3584 CT Utrecht, The Netherlands

* To whom correspondence should be addressed. Tel: +31 30 2121963; Fax: +31 30 2516554; Email: plasterk{at}niob.knaw.nl

Received October 11, 2004; Revised and Accepted November 10, 2004

MicroRNAs (miRNAs) are involved in the regulation of gene expression at the post-transcriptional level by base pairing to the 3'-UTR (untranslated region) of mRNAs. The let-7 miRNA was first discovered in Caenorhabditis elegans and is evolutionarily conserved. We used zebrafish embryos as a vertebrate in vivo system to study substrate requirements for function of let-7. Injection of a double-stranded let-7 miRNA into the zygotes of zebrafish and frogs causes specific phenotypic defects. Only the antisense strand of the let-7 duplex has biological activity. In addition, co-injected mRNA of gfp fused to the 3'-UTR of a zebrafish lin-41 ortholog (a presumed target of let-7) is silenced by let-7. Point mutant studies revealed that the two let-7 target sites in the lin-41 3'-UTR are both essential and sufficient for silencing. let-7 and mir221 together, but not either of them alone, can silence a construct with one of the let-7 target sites replaced by a target site for mir221, showing that two different miRNAs can provide the required cooperative effect. let-7 target sites can be moved around: they are also functional when positioned in the coding sequence or even in the 5'-UTR of gfp. We took advantage of reporter and phenotypic assays to analyze the activity of all possible point mutant derivatives of let-7 and found that only the 5' region is critical for function of let-7.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
N. Li, A. S. Flynt, H. R. Kim, L. Solnica-Krezel, and J. G. Patton
Dispatched Homolog 2 is targeted by miR-214 through a combination of three weak microRNA recognition sites
Nucleic Acids Res., August 1, 2008; 36(13): 4277 - 4285.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
W.-F. Shen, Y.-L. Hu, L. Uttarwar, E. Passegue, and C. Largman
MicroRNA-126 Regulates HOXA9 by Binding to the Homeobox
Mol. Cell. Biol., July 15, 2008; 28(14): 4609 - 4619.
[Abstract] [Full Text] [PDF]

Home page
 RNAHome page
A. M. Duursma, M. Kedde, M. Schrier, C. le Sage, and R. Agami
miR-148 targets human DNMT3b protein coding region
RNA, May 1, 2008; 14(5): 872 - 877.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. J. Lowery, N. Miller, R. E. McNeill, and M. J. Kerin
MicroRNAs as Prognostic Indicators and Therapeutic Targets: Potential Effect on Breast Cancer Management
Clin. Cancer Res., January 15, 2008; 14(2): 360 - 365.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
A. Stark, P. Kheradpour, L. Parts, J. Brennecke, E. Hodges, G. J. Hannon, and M. Kellis
Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomes
Genome Res., December 1, 2007; 17(12): 1865 - 1879.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
Y. S. Aulchenko, J. Pullen, W. P. Kloosterman, M. Yazdanpanah, A. Hofman, N. Vaessen, P. J.L.M. Snijders, D. Zubakov, I. Mackay, M. Olavesen, et al.
LPIN2 Is Associated With Type 2 Diabetes, Glucose Metabolism, and Body Composition
Diabetes, December 1, 2007; 56(12): 3020 - 3026.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. W. Salzman, J. Shubert-Coleman, and H. Furneaux
P68 RNA Helicase Unwinds the Human let-7 MicroRNA Precursor Duplex and Is Required for let-7-directed Silencing of Gene Expression
J. Biol. Chem., November 9, 2007; 282(45): 32773 - 32779.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
Y.-C. Lin, L.-C. Hsieh, M.-W. Kuo, J. Yu, H.-H. Kuo, W.-L. Lo, R.-J. Lin, A. L. Yu, and W.-H. Li
Human TRIM71 and Its Nematode Homologue Are Targets of let-7 MicroRNA and Its Zebrafish Orthologue Is Essential for Development
Mol. Biol. Evol., November 1, 2007; 24(11): 2525 - 2534.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. R. Lytle, T. A. Yario, and J. A. Steitz
Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3' UTR
PNAS, June 5, 2007; 104(23): 9667 - 9672.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
P. Saetrom, B. S.E. Heale, O. Snove Jr, L. Aagaard, J. Alluin, and J. J. Rossi
Distance constraints between microRNA target sites dictate efficacy and cooperativity
Nucleic Acids Res., April 1, 2007; 35(7): 2333 - 2342.
[Abstract] [Full Text] [PDF]

Home page
 RNAHome page
L. M. Aleman, J. Doench, and P. A. Sharp
Comparison of siRNA-induced off-target RNA and protein effects
RNA, March 1, 2007; 13(3): 385 - 395.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
F. G. Wulczyn, L. Smirnova, A. Rybak, C. Brandt, E. Kwidzinski, O. Ninnemann, M. Strehle, A. Seiler, S. Schumacher, and R. Nitsch
Post-transcriptional regulation of the let-7 microRNA during neural cell specification
FASEB J, February 1, 2007; 21(2): 415 - 426.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Z. Yu, Z. Jian, S.-H. Shen, E. Purisima, and E. Wang
Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos
Nucleic Acids Res., January 12, 2007; 35(1): 152 - 164.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
G. D. Hayes, A. R. Frand, and G. Ruvkun
The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25
Development, December 1, 2006; 133(23): 4631 - 4641.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
M. A. Valencia-Sanchez, J. Liu, G. J. Hannon, and R. Parker
Control of translation and mRNA degradation by miRNAs and siRNAs.
Genes & Dev., March 1, 2006; 20(5): 515 - 524.
[Abstract] [Full Text] [PDF]

Home page
 RNAHome page
P. SETHUPATHY, B. CORDA, and A. G. HATZIGEORGIOU
TarBase: A comprehensive database of experimentally supported animal microRNA targets
RNA, February 1, 2006; 12(2): 192 - 197.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
W. P. Kloosterman, F. A. Steiner, E. Berezikov, E. de Bruijn, J. van de Belt, M. Verheul, E. Cuppen, and R. H.A. Plasterk
Cloning and expression of new microRNAs from zebrafish.
Nucleic Acids Res., January 1, 2006; 34(9): 2558 - 2569.
[Abstract] [Full Text] [PDF]

Home page
 RNAHome page
R. S. PILLAI
MicroRNA function: Multiple mechanisms for a tiny RNA?
RNA, December 1, 2005; 11(12): 1753 - 1761.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
L. Wu and J. G. Belasco
Micro-RNA Regulation of the Mammalian lin-28 Gene during Neuronal Differentiation of Embryonal Carcinoma Cells
Mol. Cell. Biol., November 1, 2005; 25(21): 9198 - 9208.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
E. Berezikov and R. H.A. Plasterk
Camels and zebrafish, viruses and cancer: a microRNA update
Hum. Mol. Genet., October 15, 2005; 14(suppl_2): R183 - R190.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
A. E. Rougvie
Intrinsic and extrinsic regulators of developmental timing: from miRNAs to nutritional cues
Development, September 1, 2005; 132(17): 3787 - 3798.
[Abstract] [Full Text] [PDF]

Home page
 RNAHome page
O. SAeTROM, O. SNOVE JR., and P. SAeTROM
Weighted sequence motifs as an improved seeding step in microRNA target prediction algorithms
RNA, July 1, 2005; 11(7): 995 - 1003.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. J. Giraldez, R. M. Cinalli, M. E. Glasner, A. J. Enright, J. M. Thomson, S. Baskerville, S. M. Hammond, D. P. Bartel, and A. F. Schier
MicroRNAs Regulate Brain Morphogenesis in Zebrafish
Science, May 6, 2005; 308(5723): 833 - 838.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. S. Mattick and I. V. Makunin
Small regulatory RNAs in mammals
Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R121 - R132.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.