PMID- 21991303
OWN - NLM
STAT- MEDLINE
DCOM- 20120206
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 10
DP  - 2011
TI  - Post-transcriptional regulation of Transforming Growth Factor Beta-1 by 
      microRNA-744.
PG  - e25044
LID - 10.1371/journal.pone.0025044 [doi]
LID - e25044
AB  - Transforming Growth Factor Beta-1 (TGF-beta1) is a pleiotropic cytokine that is of 
      central importance in wound healing, inflammation, and in key pathological 
      processes including cancer and progressive tissue fibrosis. TGF-beta1 is 
      post-transcriptionally regulated, but the underlying mechanisms remain 
      incompletely defined. Previously, we have extensively delineated 
      post-transcriptional regulation of TGF-beta1 synthesis in the kidney, with evidence 
      for relief of translational repression in proximal tubular cells in the context 
      of diabetic nephropathy. In this study, we have investigated the role of the 
      TGF-beta1 3'Untranslated Region (3'UTR). Two different 3'UTR lengths have been 
      reported for TGF-beta1, of 543 and 137 nucleotides. Absolute quantification showed 
      that, while both UTR lengths were detectable in various human cell types and in a 
      broad range of tissues, the short form predominated in the kidney and elsewhere. 
      Expression of both forms was up-regulated following auto-induction by TGF-beta1, but 
      the short:long UTR ratio remained constant. Incorporation of the short UTR into a 
      luciferase reporter vector significantly reduced reporter protein synthesis 
      without major effect on RNA amount, suggesting post-transcriptional inhibition. 
      In silico approaches identified multiple binding sites for miR-744 located in the 
      proximal TGF-beta1 3'UTR. A screen in RNA from human tissues showed widespread 
      miR-744 expression. miR-744 transfection inhibited endogenous TGF-beta1 synthesis, 
      while direct targeting of TGF-beta1 was shown in separate experiments, in which 
      miR-744 decreased TGF-beta1 3'UTR reporter activity. This work identifies 
      miR-744-directed post-transcriptional regulation of TGF-beta1 which, given the 
      pleiotropic nature of cellular responses to TGF-beta1, is potentially widely 
      significant.
FAU - Martin, John
AU  - Martin J
AD  - School of Medicine, Institute of Nephrology, Cardiff University, Cardiff, Wales, 
      United Kingdom.
FAU - Jenkins, Robert H
AU  - Jenkins RH
FAU - Bennagi, Rasha
AU  - Bennagi R
FAU - Krupa, Aleksandra
AU  - Krupa A
FAU - Phillips, Aled O
AU  - Phillips AO
FAU - Bowen, Timothy
AU  - Bowen T
FAU - Fraser, Donald J
AU  - Fraser DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111004
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (3' Untranslated Regions)
RN  - 0 (MIRN663 microRNA, human)
RN  - 0 (MIRN744 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Nucleotides)
RN  - 0 (Protein Isoforms)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
MH  - 3' Untranslated Regions/genetics
MH  - Base Sequence
MH  - Cell Line
MH  - Cell Nucleus/genetics
MH  - Conserved Sequence/genetics
MH  - DNA Copy Number Variations/genetics
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Genes, Reporter/genetics
MH  - Humans
MH  - MicroRNAs/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Nucleotides/genetics
MH  - Organ Specificity/genetics
MH  - Protein Isoforms/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Alignment
MH  - *Transcription, Genetic
MH  - Transfection
MH  - Transforming Growth Factor beta1/*genetics/metabolism
PMC - PMC3186795
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/10/13 06:00
MHDA- 2012/02/07 06:00
PMCR- 2011/10/04
CRDT- 2011/10/13 06:00
PHST- 2011/06/29 00:00 [received]
PHST- 2011/08/23 00:00 [accepted]
PHST- 2011/10/13 06:00 [entrez]
PHST- 2011/10/13 06:00 [pubmed]
PHST- 2012/02/07 06:00 [medline]
PHST- 2011/10/04 00:00 [pmc-release]
AID - PONE-D-11-12058 [pii]
AID - 10.1371/journal.pone.0025044 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(10):e25044. doi: 10.1371/journal.pone.0025044. Epub 2011 Oct 4.