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

Autor:	Alvarez-Dominguez JR; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA, 02142, USA.; Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA19104, USA.; Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA19104, USA., Winther S; Department of Biology, University of Copenhagen, Universitetsparken 13, DK2100, Copenhagen, Denmark., Hansen JB; Department of Biology, University of Copenhagen, Universitetsparken 13, DK2100, Copenhagen, Denmark., Lodish HF; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA, 02142, USA.; Departments of Biology and Biological Engineering, Massachusetts Institute of Technology, 21Ames Street, Cambridge, MA02142, USA., Knoll M; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA, 02142, USA.; Institute for Diabetes Research, Helmholtz Zentrum München, Heidemannstrasse 1, 80939München, Germany.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2021 Dec 25; Vol. 25 (1), pp. 103680. Date of Electronic Publication: 2021 Dec 25 (Print Publication: 2022).
DOI:	10.1016/j.isci.2021.103680
Abstrakt:	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. Competing Interests: The authors declare no competing interests. (© 2021 The Author(s).)
Databáze:	MEDLINE
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