Reference : Combinatorial regulation of lipoprotein lipase by microRNAs during mouse adipogenesis
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/15365
Combinatorial regulation of lipoprotein lipase by microRNAs during mouse adipogenesis
English
Liivrand, Maria mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Heinäniemi, Merja mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit]
John, Elisabeth mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Schneider, Jochen mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Sauter, Thomas mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Sinkkonen, Lasse mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
16-Jan-2014
RNA Biology
Landes Bioscience
11
1
76-91
Yes (verified by ORBilu)
International
1547-6286
1555-8584
Austin
USA
[en] microRNA ; mathematical modelling ; combinatorial gene regulation ; lipoprotein lipase ; adipocyte differentiation
[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.
Luxembourg Centre for Systems Biomedicine (LCSB): Medical Translational Research (J. Schneider Group)
Fonds National de la Recherche - FnR ; University of Luxembourg - UL ; Fondation National de Luxembourg (Pelican grant by Mie et Pierre Hippert-Faber)
http://hdl.handle.net/10993/15365
10.4161/rna.27655
http://www.landesbioscience.com/journals/rnabiology/article/27655/
The original publication is available from Landes Bioscience journal RNA Biology.

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
Liivrand&Sinkkonen-RNABiol2014.pdfPublisher postprint2.37 MBView/Open

Additional material(s):

File Commentary Size Access
Open access
Liivrand&Sinkkonen-RNABiol2014(SUPPLEMENTARY).pdf12.93 MBView/Open

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.