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

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An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs. / Alvarez-Dominguez, Juan R.; Winther, Sally; Hansen, Jacob B.; Lodish, Harvey F.; Knoll, Marko.

I: iScience, Bind 25, Nr. 1, 103680, 2022.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Alvarez-Dominguez, JR, Winther, S, Hansen, JB, Lodish, HF & Knoll, M 2022, 'An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs', iScience, bind 25, nr. 1, 103680. https://doi.org/10.1016/j.isci.2021.103680

APA

Alvarez-Dominguez, J. R., Winther, S., Hansen, J. B., Lodish, H. F., & Knoll, M. (2022). An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs. iScience, 25(1), [103680]. https://doi.org/10.1016/j.isci.2021.103680

Vancouver

Alvarez-Dominguez JR, Winther S, Hansen JB, Lodish HF, Knoll M. An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs. iScience. 2022;25(1). 103680. https://doi.org/10.1016/j.isci.2021.103680

Author

Alvarez-Dominguez, Juan R. ; Winther, Sally ; Hansen, Jacob B. ; Lodish, Harvey F. ; Knoll, Marko. / An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs. I: iScience. 2022 ; Bind 25, Nr. 1.

Bibtex

@article{785d056e122b46778face1dc1e3db26a,
title = "An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs",
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.",
keywords = "Biological sciences, Molecular biology, Molecular physiology, Omics",
author = "Alvarez-Dominguez, {Juan R.} and Sally Winther and Hansen, {Jacob B.} and Lodish, {Harvey F.} and Marko Knoll",
note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2022",
doi = "10.1016/j.isci.2021.103680",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - An adipose lncRAP2-Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs

AU - Alvarez-Dominguez, Juan R.

AU - Winther, Sally

AU - Hansen, Jacob B.

AU - Lodish, Harvey F.

AU - Knoll, Marko

N1 - Publisher Copyright: © 2021 The Author(s)

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Biological sciences

KW - Molecular biology

KW - Molecular physiology

KW - Omics

U2 - 10.1016/j.isci.2021.103680

DO - 10.1016/j.isci.2021.103680

M3 - Journal article

C2 - 35036870

AN - SCOPUS:85122295239

VL - 25

JO - iScience

JF - iScience

SN - 2589-0042

IS - 1

M1 - 103680

ER -

ID: 291128009