An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs
Name
1-s2.0-S2589004221016503-main.pdf
Description
Published version
Size
4.1 MB
Format
Adobe PDF
Checksum (MD5)
83f7a48325b2b11ea1bed1632fe9dddf
Author(s)
Alvarez-Dominguez, Juan R
Winther, Sally
Hansen, Jacob B
Lodish, Harvey F
Knoll, Marko
Date Issued
2022
Journal
iScience
Publisher
Elsevier BV
Citation
Alvarez-Dominguez, Juan R, Winther, Sally, Hansen, Jacob B, Lodish, Harvey F and Knoll, Marko. 2022. "An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs." iScience, 25 (1).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.ISCI.2021.103680
