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Nucleic Acids Research 2005 33(2):451-463; doi:10.1093/nar/gki186
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Published online 19 January 2005

© 2005, the authors Nucleic Acids Research, Vol. 33 No. 2 © Oxford University Press 2005; all rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use permissions, please contact journals.permissions{at}oupjournals.org.

Article

Facile FMR1 mRNA structure regulation by interruptions in CGG repeats

Marek Napierala, Daniel Michalowski, Mateusz de Mezer and Wlodzimierz J. Krzyzosiak*

Laboratory of Cancer Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences Noskowskiego 12/14 St, 61-704, Poznan, Poland

*To whom correspondence should be addressed. Tel: +48 61 8528503; Fax: +48 61 8520532; Email: wlodkrzy{at}ibch.poznan.pl

Received October 4, 2004. Revised December 10, 2004. Accepted December 21, 2004.

RNA metabolism is a major contributor to the pathogenesis of clinical disorders associated with premutation size alleles of the fragile X mental retardation (FMR1) gene. Herein, we determined the structural properties of numerous FMR1 transcripts harboring different numbers of both CGG repeats and AGG interruptions. The stability of hairpins formed by uninterrupted repeat-containing transcripts increased with the lengthening of the repeat tract. Even a single AGG interruption in the repeated sequence dramatically changed the folding of the 5'UTR fragments, typically resulting in branched hairpin structures. Transcripts containing different lengths of CGG repeats, but sharing a common AGG pattern, adopted similar types of secondary structures. We postulate that interruption-dependent structure variants of the FMR1 mRNA contribute to the phenotype diversity, observed in premutation carriers.

Present addresses: Marek Napierala, Institute of Biosciences and Technology, Center for Genome Research, Texas A & M University System Health Science Center, Texas Medical Center, Houston, Texas 77030-3303 USA

Daniel Michalowski, Human Retrovirus Pathogenesis Section, Vaccine Branch, NCI, National Institutes of Health, Frederick, Maryland 21702-1201


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