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M6a methylation drives IMP1 regulation during human neuronal differentiation [miCLIP]

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

PROVIDER: PRJNA841466 | ENA |

REPOSITORIES: ENA

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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.

2024-04-13 | GSE203570 | GEO

m6a methylation drives IMP1 regulation during human neuronal differentiation.

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

| PRJNA841463 | ENA

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

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

| PRJNA841467 | ENA

m6a methylation drives IMP1 regulation during human neuronal differentiation [RNA-seq]

Project description:m6a methylation drives IMP1 regulation during human neuronal differentiation [RNA-seq]

| PRJNA841468 | ENA

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

m6a methylation drives IMP1 regulation during human neuronal differentiation [RNA-seq]

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 | GSE203568 | GEO

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.

2024-11-01 | GSE214367 | GEO

m6A modification in effector CD4+ T cells [m6A-miCLIP-seq]

Project description:GP61-primed effector CD4+ T cells were isolated from Ctrl or Mettl3-deficient SMARTA mice. Total RNAs were extracted with TRIzol reagent, and mRNAs were then isolated with Dynabeads® mRNA purification kit, followed by stardard m6A-miCLIP-SMARTer-seq with some modifications. Raw sequencing reads were aligned to the mouse genome (mm10) with BWA, and then m6A sites were determined.

2021-01-19 | GSE129649 | GEO

Single-nucleotide resolution profiling of N6-methyladenosine in SETD2 knockdown HepG2 cells [m6A miCLIP-seq]

Project description:To understand the global effect of H3K36me3 on m6A modification, we compared the m6A profiling in SETD2 knockdown and control HepG2 cells by miCLIP-seq, and found the depletion of H3K36me3 by SETD2 silencing globally reduced m6A in the human transcriptome.

2019-02-21 | GSE121942 | GEO

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