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RBM15 Modulates the Function of Chromatin Remodeling Factor BAF155 Through RNA Methylation in Developing Cortex

  • Yuanbin XieEmail author
  • Ricardo Castro-Hernández
  • Godwin Sokpor
  • Linh Pham
  • Ramanathan Narayanan
  • Joachim Rosenbusch
  • Jochen F. Staiger
  • Tran TuocEmail author
Article

Abstract

Chromatin remodeling factor BAF155 is an important regulator of many biological processes. As a core and scaffold subunit of the BAF (SWI/SNF-like) complex, BAF155 is capable of regulating the stability and function of the BAF complex. The spatiotemporal expression of BAF155 during embryogenesis is essential for various aspects of organogenesis, particularly in the brain development. However, our understanding of the mechanisms that regulate the expression and function of BAF155 is limited. Here, we report that RBM15, a subunit of the m6A methyltransferase complex, interacts with BAF155 mRNA and mediates BAF155 mRNA degradation through the mRNA methylation machinery. Ablation of endogenous RBM15 expression in cultured neuronal cells and in the developing cortex augmented the expression of BAF155. Conversely, RBM15 overexpression decreased BAF155 mRNA and protein levels, and perturbed BAF155 functions in vivo, including repression of BAF155-dependent transcriptional activity and delamination of apical radial glial progenitors as a hallmark of basal radial glial progenitor genesis. Furthermore, we demonstrated that the regulation of BAF155 by RBM15 depends on the activity of the mRNA methylation complex core catalytic subunit METTL3. Altogether, our findings reveal a new regulatory avenue that elucidates how BAF complex subunit stoichiometry and functional modulation are achieved in mammalian cells.

Keywords

BAF (mSWI/SNF) complex BAF155 RNA methylation RNA decay RBM15 METTL3 Cortical development Basal progenitor 

Notes

Acknowledgments

We acknowledge Dr. Francois Guillemot, Dr. Diane S. Krause, Dr. Rho H. Seong, and Dr. Hongjun Song for providing reagents. This work was supported by the Research Program, Faculty of Medicine, Georg-August-University Goettingen (TT), TU432/1-1, TU432/3-1 DFG grants (TT), Schram-Stiftung (TT), and DFG-CNMPB (TT, JFS).

Author Contributions

Y.X, R.C.H, G.S, L.P, J.R performed experiments and analyzed data; R.N contributed to luciferase assay; Y.X, T.T designed experiments; J.F.S provided research tools and contributed to discussions. The authors declare no competing financial interests.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

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ESM 1 (DOCX 2141 kb)
12035_2019_1595_MOESM2_ESM.xls (408 kb)
ESM 2 (XLS 407 kb)

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Authors and Affiliations

  1. 1.Institute for Neuroanatomy, University Medical CenterGeorg-August-University GoettingenGoettingenGermany
  2. 2.DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)GoettingenGermany
  3. 3.Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and TechnologySwiss Federal Institute of Technology (ETH)ZurichSwitzerland

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