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M6a methylation drives IMP1 regulation during human neuronal differentiation [RNA-seq]

ABSTRACT: Human neurodevelopment requires differentiating neurons to establish large networks of connections in a highly stereotyped manner. Neuronal differentiation in particular requires RNA-binding proteins to spatiotemporally regulate thousands of different mRNAs. Yet how these proteins precisely relate to neuronal development and coordinate the expression of functionally coherent genes in a cell type specific manner is only partially understood. To address this, we sought to clarify how the paradigmatic RNA-binding protein IMP1/IGF2BP1, an essential developmental factor, selects and regulates its RNA targets transcriptome-wide during the differentiation of human pluripotent stem cell-derived neural precursor cells to their neuronal counterparts. We used a combination of systemic and molecular analyses to show that IMP1 directly binds to and regulates the expression of a large sets of mRNAs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE203568 | GEO | 2024/04/13

REPOSITORIES: GEO

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m6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation

Project description:Human neurodevelopment requires differentiating neurons to establish large networks of connections in a highly stereotyped manner. Neuronal differentiation in particular, requires RNA-binding proteins to spatiotemporally regulate thousands of different mRNAs. Yet, how these proteins precisely relate to neuronal development and coordinate the expression of functionally coherent genes in a cell type specific manner is only partially understood. To address this, we sought to understand how the paradigmatic RNA-binding protein IMP1/IGF2BP1, an essential developmental factor, selects and regulates its RNA targets transcriptome-wide during the differentiation of human neurons. We used a combination of systemic and molecular analyses to show that IMP1 directly binds to and regulates the expression of a large set of mRNAs that govern microtubule assembly, an essential process and a key driver of neuronal differentiation. We also show that m6A methylation during the transition from neural precursors to neurons drives both the selection of IMP1 mRNA targets and their translation potential. Our findings establish m6A methylation as a key mechanism coordinating the regulatory action of IMP1 on human neuronal architecture.

2024-06-10 | PXD034341 | Pride

m6a methylation drives IMP1 regulation during human neuronal differentiation [miCLIP]

Project description:Human neurodevelopment requires differentiating neurons to establish large networks of connections in a highly stereotyped manner. Neuronal differentiation in particular requires RNA-binding proteins to spatiotemporally regulate thousands of different mRNAs. Yet how these proteins precisely relate to neuronal development and coordinate the expression of functionally coherent genes in a cell type specific manner is only partially understood. To address this, we sought to clarify how the paradigmatic RNA-binding protein IMP1/IGF2BP1, an essential developmental factor, selects and regulates its RNA targets transcriptome-wide during the differentiation of human pluripotent stem cell-derived neural precursor cells to their neuronal counterparts. We used a combination of systemic and molecular analyses to show that IMP1 directly binds to and regulates the expression of a large sets of mRNAs.

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m6a methylation drives IMP1 regulation during human neuronal differentiation [iCLiP]

Project description:Human neurodevelopment requires differentiating neurons to establish large networks of connections in a highly stereotyped manner. Neuronal differentiation in particular requires RNA-binding proteins to spatiotemporally regulate thousands of different mRNAs. Yet how these proteins precisely relate to neuronal development and coordinate the expression of functionally coherent genes in a cell type specific manner is only partially understood. To address this, we sought to clarify how the paradigmatic RNA-binding protein IMP1/IGF2BP1, an essential developmental factor, selects and regulates its RNA targets transcriptome-wide during the differentiation of human pluripotent stem cell-derived neural precursor cells to their neuronal counterparts. We used a combination of systemic and molecular analyses to show that IMP1 directly binds to and regulates the expression of a large sets of mRNAs.

2024-04-13 | GSE203569 | GEO

Long Noncoding RNA Expression profiling of IMP1-expression and IMP1 nonexpression MDA231 Cells

Project description:ZBP1/IMP1 is a RNA binding protein that post-transcriptionally regulates the expression of a handful mRNAs, implicated in maintaining cell polarity and adhesion. We have previously shown that ZBP1 was able to inhibit proliferation and invasiveness of breast carcinoma cells in vitro. To determine important LncRNA for breast tumor growth and metastasis in response to IMP1 expression, LncRNA expression data were obtained from, and compared between the breast cancer cell line MDA231-IMP1 and MDA231/GFP.

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Chromatin immunoprecipitation of human HEK293 cells with flag-tagged IMP1 antibody

Project description:Isolation of IMP1 bound mRNAs. Flag-tagged IMP1 was expressed in HEK293 cells. Flag tagged IMP1 was immunoprecipitated and mRNAs isolated. As controls HEK293 cells that do not express Flag-tagged IMP1 was included.

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Recognition of m6A RNA by the non-canonical reader IMP1

Project description:m6A methylation is the prevalent post-transcriptional modification in eukaryotic mRNAs and provides an essential layer of regulation in organismal development and in disease. The information encoded by m6A methylation is integrated into existing RNA regulatory networks by the binding of an expanding list of m6A readers. An important question is how protein readers that do not contain a canonical m6A-specific YTH domain recognize methylated RNA. Here, we show that the non-canonical reader IMP1 directly recognises the m6A group using a dedicated hydrophobic platform in the KH4 domain, creating a stable and high affinity interaction with the methylated RNA targets. Notably, the recognition of the m6A group is independent from the underlying sequence context, but is layered upon IMP1 strong sequence specificity for GGAC RNA. Together, our data indicate that, contrarily to the well-characterised YTH readers, IMP1 recognises and binds both m6A-methylated and non-methylated RNA targets with high affinity. This suggests that m6A methylation does not provide a general layer of control of IMP1 function, but rather plays a directed role in specific regulatory pathways.

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IMP1 re-expression in adult hematopoietic stem cells RNA Sequencing

Project description:The onco-fetal RNA-binding protein IMP1 is expressed in fetal liver HSCs, but down-regulated in adult BM HSCs. We here show that when IMP1 is re-expressed in adult HSCs it induces a significant part of the fetal HSC gene expression signature. In addition, IMP1 re-expression leads to the expansion of phenotypic long term (LT-)HSCs, and increased generation of fetal peritoneal B1a B-cells and thymic γδ-T-cells. Finally, IMP1 expressing adult LT-HSCs show dramatically improved self-renewal in serial transplantations compared to their normal counterparts. To assess the effect of IMP1 re-expression on the molecular properties of adult HSCs we performed RNA sequencing of total RNA isolated from Control and IMP1 HSCs sorted from primary recipient mice, transplanted with control or IMP1+ total bone marrow cells.

2018-12-21 | GSE76243 | GEO

IMP1/IGF2BP1 enters extracellular vesicles in colorectal cancer

Project description:IMP1/IGF2BP1 enters extracellular vesicles in colorectal cancer

2022-09-30 | GSE198804 | GEO

m6a methylation drives IMP1 regulation during human neuronal differentiation.

Project description:m6a methylation drives IMP1 regulation during human neuronal differentiation.

| PRJNA841463 | ENA

Identification of Target LncRNAs of IMP1 in T47D Cells by RIP-Seq technique

Project description:IMP1 is a RNA binding protein shown to regulate translation, localization, or stability of their target RNAs. However, whether IMP1 can widely bind to lncRNAs and regulate their expression in Breast cancer cells remains to be confirmed. In this study, we used RNA binding protein immunoprecipitation-high throughput sequencing (RIP-Seq) technique to identify LncRNAs which bind to IMP1 protein in breast cancer cell line T47D cells.

2023-06-08 | GSE220087 | GEO

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