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An adipose lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs [RIP-seq]

ABSTRACT: An adipose lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs [RIP-seq]

PROVIDER: PRJNA792801 | ENA |

REPOSITORIES: ENA

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An adipose lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs [RIP-seq]

Project description: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.

2021-12-31 | GSE192705 | GEO

An adipose lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs [RNA-seq]

2021-12-04 | GSE190047 | GEO

An adipose lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs [RIA-seq]

2021-12-31 | GSE192704 | GEO

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

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

| PRJNA792797 | ENA

An adipose lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs [RIA-seq]

Project description:An adipose lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs [RIA-seq]

| PRJNA792802 | ENA

An adipose lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs [RNA-seq]

Project description:An adipose lncRAP2 - Igf2bp2 complex enhances adipogenesis and energy expenditure by stabilizing target mRNAs [RNA-seq]

| PRJNA785633 | ENA

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

Project description: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.

| S-EPMC8749451 | biostudies-literature

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

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-12-30 | GSE192706 | GEO

Dynamics of m6A RNA methylome during leukemogenesis reveals a role of IGF2BP2-PRMT6-MFSD2A signaling axis in maintaining AML stem cells [IGF2BP2 RNA-seq]

Project description:Our data reveal that RNA m6A displays a sharp transition during leukemogenesis and involves in acquiring stem cell properties of leukemia stem cells (LSCs). We find that m6A reader IGF2BP2 and protein arginine methyltransferase PRMT6 play key roles in the acquisition of LSCs properties. Genetical deletion and pharmacological inhibition of PRMT6 delayed AML development. Mechanistically, IGF2BP2 regulates PRMT6 expression by stabilizing its mRNA in an m6A-dependent manner. PRMT6 further suppresses the expression of lipid transporter MFSD2A by establishing inactive H3R2me2a in its promoter region. Loss of PRMT6 and IGF2BP2 upregulates the expression of MFSD2A that increases the uptake of docosahexaenoic acid. Collectively, our findings uncover a critical role of IGF2BP2-PRMT6-MFSD2A signaling axis in AML development, and provide a promising therapeutic strategy for targeting LSCs.

2023-06-20 | GSE210278 | GEO

The m6A reader IGF2BP2 regulates macrophage phenotypic activation and inflammatory diseases by stabilizing TSC1 and PPARγ

Project description:Phenotypic polarization of macrophages is regulated by a milieu of cues in the local tissue microenvironment. Currently, little is known about how the intrinsic regulators modulate pro-inflammatory (M1) versus pro-healing (M2) macrophages activation. Here, we observed that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) -deleted macrophages exhibited enhanced M1 phenotype and promoted DSS induced colitis development. However, the IGF2BP2-/- macrophages were refractory to IL4 induced activation and alleviated cockroach extract induced pulmonary allergic inflammation. Molecular studies indicated IGF2BP2 switched M1 macrophages to M2 activation by targeting tuberous sclerosis 1 (TSC1) via an N6-methyladenosine-dependent manner. Additionally, we also showed a signal transducer and activators of transcription 6 (STAT6) - high mobility group AT-hook 2 (HMGA2) -IGF2BP2-peroxisome proliferator activated receptor-γ (PPARγ) axis involves in M2 macrophages differentiation. These findings highlight a key role of IGF2BP2 in regulation of macrophages activation and imply a potential therapeutic target of macrophages in the inflammatory diseases.

2021-03-15 | GSE162128 | GEO

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