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Alvarez-Dominguez, J.R.* ; Winther, S.* ; Hansen, J.B.* ; Lodish, H.F.* ; Knoll, M.

An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs.

iScience 25:103680 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
lncRAP2 is a conserved cytoplasmic lncRNA enriched in adipose tissue and required for adipogenesis. Using purification and in vivo interactome analyses, we show that lncRAP2 forms complexes with proteins that stabilize mRNAs and modulate translation, among them Igf2bp2. Surveying transcriptome-wide Igf2bp2 client mRNAs in white adipocytes reveals selective binding to mRNAs encoding adipogenic regulators and energy expenditure effectors, including adiponectin. These same target proteins are downregulated when either Igf2bp2 or lncRAP2 is downregulated, hindering adipocyte lipolysis. Proteomics and ribosome profiling show this occurs predominantly through mRNA accumulation, as lncRAP2-Igf2bp2 complex binding does not impact translation efficiency. Phenome-wide association studies reveal specific associations of genetic variants within both lncRAP2 and Igf2bp2 with body mass and type 2 diabetes, and both lncRAP2 and Igf2bp2 are suppressed in adipose depots of obese and diabetic individuals. Thus, the lncRAP2-Igf2bp2 complex potentiates adipose development and energy expenditure and is associated with susceptibility to obesity-linked diabetes.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Biological Sciences ; Molecular Biology ; Molecular Physiology ; Omics; Long Noncoding Rnas; Genome-wide Association; Body-mass Index; Binding-protein; Gene-expression; Tissue; Translation; Regulators; Loci; Discovery
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Zeitschrift iScience
Quellenangaben Band: 25, Heft: 1, Seiten: , Artikelnummer: 103680 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research (IDF)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502100-001
Förderungen National Institute of Health
Deutsche Forschungsgemeinschaft
DOI 10.1016/j.isci.2021.103680
WOS ID WOS:000766675800010
Scopus ID 85122295239
PubMed ID 35036870
Erfassungsdatum 2022-05-31
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