PMID- 25274779
OWN - NLM
STAT- MEDLINE
DCOM- 20150922
LR  - 20150126
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 24
IP  - 4
DP  - 2015 Feb 15
TI  - CFTR mRNA expression is regulated by an upstream open reading frame and RNA 
      secondary structure in its 5' untranslated region.
PG  - 899-912
LID - 10.1093/hmg/ddu501 [doi]
AB  - Post-transcriptional regulation of gene expression through 5' untranslated region 
      (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 while remaining responsive to 
      cellular requirements. With respect to cystic fibrosis (CF), the overexpression 
      of cystic fibrosis transmembrane conductance regulator (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 CF 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.
CI  - (c) The Author 2014. Published by Oxford University Press. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Lukowski, Samuel W
AU  - Lukowski SW
AD  - School of Chemistry and Molecular Biosciences and Australian Equine Genetics 
      Research Centre, The University of Queensland, Brisbane, QLD 4072, Australia 
      samuel.lukowski@unige.ch.
FAU - Rothnagel, Joseph A
AU  - Rothnagel JA
AD  - School of Chemistry and Molecular Biosciences and.
FAU - Trezise, Ann E O
AU  - Trezise AE
AD  - School of Chemistry and Molecular Biosciences and Australian Equine Genetics 
      Research Centre, The University of Queensland, Brisbane, QLD 4072, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140930
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (5' Untranslated Regions)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Spliced Leader)
RN  - 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
SB  - IM
MH  - *5' Untranslated Regions
MH  - Amino Acid Sequence
MH  - Base Composition
MH  - Base Sequence
MH  - Cell Line
MH  - Computational Biology/methods
MH  - Cystic Fibrosis Transmembrane Conductance Regulator/chemistry/*genetics
MH  - Gene Expression
MH  - *Gene Expression Regulation
MH  - Genes, Reporter
MH  - Humans
MH  - Mutation
MH  - *Nucleic Acid Conformation
MH  - *Open Reading Frames
MH  - Peptide Chain Initiation, Translational
MH  - RNA Stability
MH  - RNA, Messenger/chemistry/*genetics
MH  - RNA, Spliced Leader
MH  - Thermodynamics
EDAT- 2014/10/03 06:00
MHDA- 2015/09/24 06:00
CRDT- 2014/10/03 06:00
PHST- 2014/10/03 06:00 [entrez]
PHST- 2014/10/03 06:00 [pubmed]
PHST- 2015/09/24 06:00 [medline]
AID - ddu501 [pii]
AID - 10.1093/hmg/ddu501 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2015 Feb 15;24(4):899-912. doi: 10.1093/hmg/ddu501. Epub 2014 Sep 
      30.