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M6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation

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 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Graeme Benstead-Hume

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD034341 | Pride | 2024-06-10

REPOSITORIES: Pride

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	20210419_PK_UCL_LMS03_set01_01.raw	Raw
	20210419_PK_UCL_LMS03_set01_02.raw	Raw
	20210419_PK_UCL_LMS03_set01_03.raw	Raw
	20210419_PK_UCL_LMS03_set01_04.raw	Raw
	20210419_PK_UCL_LMS03_set01_05.raw	Raw

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