Article (Scientific journals)
Combinatorial regulation of lipoprotein lipase by microRNAs during mouse adipogenesis
Liivrand, Maria; Heinäniemi, Merja; John, Elisabeth et al.
2014In RNA Biology, 11 (1), p. 76-91
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Keywords :
microRNA; mathematical modelling; combinatorial gene regulation; lipoprotein lipase; adipocyte differentiation
Abstract :
[en] MicroRNAs (miRNAs) regulate gene expression directly through base pairing to their targets or indirectly through participating in multi-scale regulatory networks. Often miRNAs take part in feed-forward motifs where a miRNA and a transcription factor act on shared targets to achieve accurate regulation of processes such as cell differentiation. Here we show that the expression levels of miR-27a and miR-29a inversely correlate with the mRNA levels of lipoprotein lipase (Lpl), their predicted combinatorial target, and its key transcriptional regulator peroxisome proliferator activated receptor gamma (Pparg) during 3T3-L1 adipocyte differentiation. More importantly, we show that Lpl, a key lipogenic enzyme, can be negatively regulated by the two miRNA families in a combinatorial fashion on the mRNA and functional level in maturing adipocytes. This regulation is mediated through the Lpl 3′UTR as confirmed by reporter gene assays. In addition, a small mathematical model captures the dynamics of this feed-forward motif and predicts the changes in Lpl mRNA levels upon network perturbations. The obtained results might offer an explanation to the dysregulation of LPL in diabetic conditions and could be extended to quantitative modeling of regulation of other metabolic genes under similar regulatory network motifs.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Medical Translational Research (J. Schneider Group)
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Liivrand, Maria ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Heinäniemi, Merja ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
John, Elisabeth ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Schneider, Jochen ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Sauter, Thomas ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Sinkkonen, Lasse  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
no
Language :
English
Title :
Combinatorial regulation of lipoprotein lipase by microRNAs during mouse adipogenesis
Publication date :
16 January 2014
Journal title :
RNA Biology
ISSN :
1555-8584
Publisher :
Landes Bioscience, Austin, United States
Volume :
11
Issue :
1
Pages :
76-91
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FNR - Fonds National de la Recherche [LU]
University of Luxembourg - UL
Fondation National de Luxembourg (Pelican grant by Mie et Pierre Hippert-Faber)
Available on ORBilu :
since 06 February 2014

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