Molecular interactome of HNRNPU reveals regulatory networks in neuronal differentiation and DNA methylation DOI Creative Commons
Marika Oksanen, Francesca Mastropasqua, Krystyna Mazan-Mamczarz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

ABSTRACT HNRNPU is an RNA-binding protein with diverse roles in regulating gene expression. Pathogenic genetic variants of cause a severe neurodevelopmental disorder (NDD), but the underlying molecular mechanisms are unclear. Here, we investigated protein-protein interaction (PPI) network and RNA targets neuroepithelial stem cells (NES) differentiating neural derived from human induced pluripotent cells. Using high-throughput approaches, found interacting mammalian SWI/SNF complex highlight its putative role multiple stages mRNA regulation. Notably, both PPI partners mRNAs implicated translation, that had not been recognized before. Also, associated encoding proteins important for neuronal development. Based on our findings, propose regulatory model which HNRNPU, coordination SWI/SNF, modulates levels accessibility DNA methylation factors, leading to global differences deficiency states, as validated cell model. This mechanism provides link distinct signature seen individuals HNRNPU-related NDDs well crucial epigenetic regulation during early brain

Language: Английский

Molecular interactome of HNRNPU reveals regulatory networks in neuronal differentiation and DNA methylation DOI Creative Commons
Marika Oksanen, Francesca Mastropasqua, Krystyna Mazan-Mamczarz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

ABSTRACT HNRNPU is an RNA-binding protein with diverse roles in regulating gene expression. Pathogenic genetic variants of cause a severe neurodevelopmental disorder (NDD), but the underlying molecular mechanisms are unclear. Here, we investigated protein-protein interaction (PPI) network and RNA targets neuroepithelial stem cells (NES) differentiating neural derived from human induced pluripotent cells. Using high-throughput approaches, found interacting mammalian SWI/SNF complex highlight its putative role multiple stages mRNA regulation. Notably, both PPI partners mRNAs implicated translation, that had not been recognized before. Also, associated encoding proteins important for neuronal development. Based on our findings, propose regulatory model which HNRNPU, coordination SWI/SNF, modulates levels accessibility DNA methylation factors, leading to global differences deficiency states, as validated cell model. This mechanism provides link distinct signature seen individuals HNRNPU-related NDDs well crucial epigenetic regulation during early brain

Language: Английский

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