Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (251K) 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 (8)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Raca, G.
Right arrow Articles by Mirkin, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Raca, G.
Right arrow Articles by Mirkin, S. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2000, Vol. 28, No. 20 3943-3949
© 2000 Oxford University Press

Expansion of the (CTG)n repeat in the 5'-UTR of a reporter gene impedes translation

Gordana Raca, Elena Yu. Siyanova, Cynthia T. McMurray1 and Sergei M. Mirkin*

Department of Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA and 1Department of Pharmacology, Mayo Clinic, Rochester, MN 55905, USA

Effects of d(CAG)n·d(CTG)n repeats on expression of a reporter gene in human cell culture were studied using transient transfection, RNase protection and coupled transcription/translation assays. Cloning these repeats into the reporter 3'-UTR did not affect gene functioning. In contrast, placing the repeats in the reporter 5'-UTR led to strong inhibition of expression. This inhibition depended on the repeat orientation, being prominent only when the (CTG)n tracts were in the sense strand for transcription. Further, the strength of inhibition increased exponentially with an increase in repeat length. Our data indicate that expanded (CTG)n repeats prevent efficient translation of the reporter mRNA both in vitro and in vivo. We suggest that formation of stable hairpins by (CUG)n runs of increasing length in the 5'-UTR of a mRNA progressively inhibits the scanning step of translation initiation. This points to a novel mechanism of regulating gene expression by expandable d(CTG)n repeats.

* To whom correspondence should be addressed. Tel: +1 312 996 9610; Fax: +1 312 413 0353; Email: mirkin@uic.edu


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
A. Kiliszek, R. Kierzek, W. J. Krzyzosiak, and W. Rypniewski
Structural insights into CUG repeats containing the 'stretched U-U wobble': implications for myotonic dystrophy
Nucleic Acids Res., July 1, 2009; 37(12): 4149 - 4156.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
K. Usdin
The biological effects of simple tandem repeats: Lessons from the repeat expansion diseases
Genome Res., July 1, 2008; 18(7): 1011 - 1019.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
M. M. Krasilnikova, M. L. Kireeva, V. Petrovic, N. Knijnikova, M. Kashlev, and S. M. Mirkin
Effects of Friedreich's ataxia (GAA)n{middle dot}(TTC)n repeats on RNA synthesis and stability
Nucleic Acids Res., February 28, 2007; 35(4): 1075 - 1084.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
Y.-C. Li, A. B. Korol, T. Fahima, and E. Nevo
Microsatellites Within Genes: Structure, Function, and Evolution
Mol. Biol. Evol., June 1, 2004; 21(6): 991 - 1007.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
A. Jasinska, G. Michlewski, M. de Mezer, K. Sobczak, P. Kozlowski, M. Napierala, and W. J. Krzyzosiak
Structures of trinucleotide repeats in human transcripts and their functional implications
Nucleic Acids Res., October 1, 2003; 31(19): 5463 - 5468.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Shchors, F. Yehiely, R. K. Kular, K. U. Kotlo, G. Brewer, and L. P. Deiss
Cell Death Inhibiting RNA (CDIR) Derived from a 3'-Untranslated Region Binds AUF1 and Heat Shock Protein 27
J. Biol. Chem., November 27, 2002; 277(49): 47061 - 47072.
[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.