CFTR mRNA expression is regulated by an upstream open reading frame and RNA secondary structure in its 5' untranslated region

Lukowski, Samuel W., Rothnagel, Joseph A. and Trezise, Ann E. O. (2014) CFTR mRNA expression is regulated by an upstream open reading frame and RNA secondary structure in its 5' untranslated region. Human Molecular Genetics, 24 4: 899-912. doi:10.1093/hmg/ddu501

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Author Lukowski, Samuel W.
Rothnagel, Joseph A.
Trezise, Ann E. O.
Title CFTR mRNA expression is regulated by an upstream open reading frame and RNA secondary structure in its 5' untranslated region
Formatted title
CFTR mRNA expression is regulated by an upstream open reading frame and RNA secondary structure in its 5 ́ untranslated region
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2014-10-13
Year available 2014
Sub-type Article (original research)
DOI 10.1093/hmg/ddu501
Open Access Status
Volume 24
Issue 4
Start page 899
End page 912
Total pages 14
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2015
Language eng
Formatted abstract
Post-transcriptional regulation of gene expression through 5 ́UTR-encoded cis-acting elements is an important mechanism for the control of protein expression levels. Through controlling specific aspects of translation initiation, expression can be tightly regulated whilst remaining responsive to cellular requirements. With respect to Cystic Fibrosis, the overexpression of CFTR protein trafficking mutants, such as delta-F508, is of great biological and clinical interest. By understanding the post-transcriptional mechanisms that regulate CFTR expression, new procedures can be developed to enhance CFTR expression in homozygous delta-F508 cystic fibrosis patients. We have identified the key elements of a complex negative regulatory mechanism that is encoded within the human CFTR 5 ́UTR and show how these elements act in combination to restrict CFTR gene expression to a consistently low level in a transcript-specific manner. This study shows, for the first time, that endogenous human CFTR expression is post-transcriptionally regulated through a 5 ́UTR-mediated mechanism. We show that the very low levels of endogenous CFTR expression, compared with other low expression genes, are maintained through the co- operative inhibitory effects of an upstream open reading frame and a thermodynamically stable RNA secondary structure.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First published online: September 30, 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
Australian Equine Genetics Research Centre Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 10 Oct 2014, 10:06:04 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences