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

Area of Science:

• Molecular Biology
• Developmental Biology
• Epigenetics

Background:

• BAF155 is a core subunit of the BAF (SWI/SNF-like) complex, crucial for chromatin remodeling and organogenesis, especially brain development.
• The precise regulation of BAF155 expression and function during embryogenesis remains incompletely understood.

Purpose of the Study:

• To investigate the regulatory mechanisms controlling BAF155 expression and function.
• To identify novel factors interacting with BAF155 mRNA and influencing its stability.

Main Methods:

• Investigated the interaction between RBM15 and BAF155 mRNA.
• Utilized cell culture and in vivo models (developing cortex) to study RBM15's effects on BAF155.
• Assessed BAF155-dependent transcriptional activity and progenitor cell delamination.
• Examined the role of METTL3 in RBM15-mediated BAF155 regulation.

Main Results:

• RBM15 interacts with BAF155 mRNA and promotes its degradation through mRNA methylation.
• RBM15 depletion increases BAF155 expression in neuronal cells and the developing cortex.
• RBM15 overexpression reduces BAF155 levels and impairs its functions, including transcriptional activity and radial glial progenitor delamination.
• RBM15's regulatory effect on BAF155 is dependent on METTL3 activity.

Conclusions:

• RBM15 acts as a negative regulator of BAF155 expression via mRNA methylation.
• This pathway provides a novel mechanism for controlling BAF complex subunit stoichiometry and function.
• Findings elucidate a new layer of gene regulation impacting mammalian development.