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Mol. Cells 2022; 45(8): 588-602

Published online August 31, 2022

https://doi.org/10.14348/molcells.2022.0044

© The Korean Society for Molecular and Cellular Biology

RNA Binding Protein Rbms1 Enables Neuronal Differentiation and Radial Migration during Neocortical Development by Binding and Stabilizing the RNA Message for Efr3a

Khadija Habib , Kausik Bishayee , Jieun Kang , Ali Sadra *, and Sung-Oh Huh *

Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon 24252, Korea

Correspondence to : s0huh@hallym.ac.kr(SOH); alisadra@hallym.ac.kr(AS)

Received: March 18, 2022; Revised: April 6, 2022; Accepted: April 9, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

Various RNA-binding proteins (RBPs) are key components in RNA metabolism and contribute to several neurodevelop­mental disorders. To date, only a few of such RBPs have been characterized for their roles in neocortex development. Here, we show that the RBP, Rbms1, is required for radial migration, polarization and differentiation of neuronal progenitors to neurons in the neocortex development. Rbms1 expression is highest in the early development in the developing cortex, with its expression gradually diminishing from embryonic day 13.5 (E13.5) to postnatal day 0 (P0). From in utero electroporation (IUE) experiments when Rbms1 levels are knocked down in neuronal progenitors, their transition from multipolar to bipolar state is delayed and this is accompanied by a delay in radial migration of these cells. Reduced Rbms1 levels in vivo also reduces differentiation as evidenced by a decrease in levels of several differentiation markers, meanwhile having no significant effects on proliferation and cell cycle rates of these cells. As an RNA binding protein, we profiled the RNA binders of Rbms1 by a cross-linked-RIP sequencing assay, followed by quantitative real-time polymerase chain reaction verification and showed that Rbms1 binds and stabilizes the mRNA for Efr3a, a signaling adapter protein. We also demonstrate that ectopic Efr3a can recover the cells from the migration defects due to loss of Rbms1, both in vivo and in vitro migration assays with cultured cells. These imply that one of the functions of Rbms1 involves the stabilization of Efr3a RNA message, required for migration and maturation of neuronal progenitors in radial migration in the developing neocortex.

Keywords Efr3a, neurogenesis, radial migration, RNA binding motif single stranded interacting protein 1

Article

Research Article

Mol. Cells 2022; 45(8): 588-602

Published online August 31, 2022 https://doi.org/10.14348/molcells.2022.0044

Copyright © The Korean Society for Molecular and Cellular Biology.

RNA Binding Protein Rbms1 Enables Neuronal Differentiation and Radial Migration during Neocortical Development by Binding and Stabilizing the RNA Message for Efr3a

Khadija Habib , Kausik Bishayee , Jieun Kang , Ali Sadra *, and Sung-Oh Huh *

Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chuncheon 24252, Korea

Correspondence to:s0huh@hallym.ac.kr(SOH); alisadra@hallym.ac.kr(AS)

Received: March 18, 2022; Revised: April 6, 2022; Accepted: April 9, 2022

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/.

Abstract

Various RNA-binding proteins (RBPs) are key components in RNA metabolism and contribute to several neurodevelop­mental disorders. To date, only a few of such RBPs have been characterized for their roles in neocortex development. Here, we show that the RBP, Rbms1, is required for radial migration, polarization and differentiation of neuronal progenitors to neurons in the neocortex development. Rbms1 expression is highest in the early development in the developing cortex, with its expression gradually diminishing from embryonic day 13.5 (E13.5) to postnatal day 0 (P0). From in utero electroporation (IUE) experiments when Rbms1 levels are knocked down in neuronal progenitors, their transition from multipolar to bipolar state is delayed and this is accompanied by a delay in radial migration of these cells. Reduced Rbms1 levels in vivo also reduces differentiation as evidenced by a decrease in levels of several differentiation markers, meanwhile having no significant effects on proliferation and cell cycle rates of these cells. As an RNA binding protein, we profiled the RNA binders of Rbms1 by a cross-linked-RIP sequencing assay, followed by quantitative real-time polymerase chain reaction verification and showed that Rbms1 binds and stabilizes the mRNA for Efr3a, a signaling adapter protein. We also demonstrate that ectopic Efr3a can recover the cells from the migration defects due to loss of Rbms1, both in vivo and in vitro migration assays with cultured cells. These imply that one of the functions of Rbms1 involves the stabilization of Efr3a RNA message, required for migration and maturation of neuronal progenitors in radial migration in the developing neocortex.

Keywords: Efr3a, neurogenesis, radial migration, RNA binding motif single stranded interacting protein 1

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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