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

Xie, Yuanbin; Castro-Hernández, Ricardo; Sokpor, Godwin; Pham, Linh; Narayanan, Ramanathan; Rosenbusch, Joachim; Staiger, Jochen F.; Tuoc, Tran

doi:10.1007/s12035-019-1595-1

Cited by 48 publications

(58 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, regulatory mechanisms of BAF155 gene expression and upstream factors of BAF155 are largely unknown. Most recently, it was found that RBM15, a subunit of the m6A methyltransferase complex, interacts with BAF155 mRNA and mediates BAF155 mRNA degradation through the mRNA methylation machinery [34]. Our observation that treatment with the proteasome inhibitor MG132 enhanced BAF155-induced HBx levels or rescued the reduction of HBx due to BAF155 knockdown further supports the concept that BAF155 is important for maintaining cellular pools of HBx and that upon loss of this protection HBx is targeted for proteasomal degradation.…”

Section: Discussionsupporting

confidence: 80%

Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation

Chen

Zhang

et al. 2019

Emerging Microbes & Infections

View full text Add to dashboard Cite

HBx is a short-lived protein whose rapid turnover is mainly regulated by ubiquitin-dependent proteasomal degradation pathways. Our prior work identified BAF155 to be one of the HBx binding partners. Since BAF155 has been shown to stabilize other members of the SWI/SNF chromatin remodelling complex by attenuating their proteasomal degradation, we proposed that BAF155 might also contribute to stabilizing HBx protein in a proteasome-dependent manner. Here we report that BAF155 protected hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation by competing with the 20S proteasome subunit PSMA7 to bind to HBx. BAF155 was found to directly interact with HBx via binding of its SANT domain to the HBx region between amino acid residues 81 and 120. Expression of either full-length BAF155 or SANT domain increased HBx protein levels whereas siRNA-mediated knockdown of endogenous BAF155 reduced HBx protein levels. Increased HBx stability and steady-state level by BAF155 were attributable to inhibition of ubiquitin-independent and PSMA7-mediated protein degradation. Consequently, overexpression of BAF155 enhanced the transcriptional transactivation function of HBx, activated protooncogene expression and inhibited hepatoma cell clonogenicity. These results suggest that BAF155 plays important roles in ubiquitin-independent degradation of HBx, which may be related to the pathogenesis and carcinogenesis of HBV-associated HCC.

show abstract

Section: Discussionsupporting

confidence: 80%

Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation

Chen

Zhang

et al. 2019

Emerging Microbes & Infections

View full text Add to dashboard Cite

show abstract

“…Forced expression via in utero electroporation in the mouse yet again boosted Tbr2+ IPs and Pax6+ bRG-like cells in the mouse cortex. Finally, to further characterize how bRG production may be regulated by Baf155, Tuoc lab’s studied how RNA methylation might impact Baf155 mRNA stability (Zhao et al, 2016; Xie et al, 2019). They showed that RNA-binding motif protein 15 (RBM15) binds to and enriches m6a methylation, and in the mouse developing cortex, high levels of Rbm15 and low levels of Baf155 were found in the IZ and CP, and the converse situation in the VZ and SVZ, suggesting that methylation of Baf155 transcripts by Rbm15 may negatively regulate their half-life.…”

Section: Molecular Mechanisms Associated With the Generation And Amplmentioning

confidence: 99%

Genes and Mechanisms Involved in the Generation and Amplification of Basal Radial Glial Cells

Penisson

Ladewig

Belvindrah

et al. 2019

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The development of the cerebral cortex relies on different types of progenitor cell. Among them, the recently described basal radial glial cell (bRG) is suggested to be of critical importance for the development of the brain in gyrencephalic species. These cells are highly numerous in primate and ferret brains, compared to lissencephalic species such as the mouse in which they are few in number. Their somata are located in basal subventricular zones in gyrencephalic brains and they generally possess a basal process extending to the pial surface. They sometimes also have an apical process directed toward the ventricular surface, similar to apical radial glial cells (aRGs) from which they are derived, and whose somata are found more apically in the ventricular zone. bRGs share similarities with aRGs in terms of gene expression ( SOX2 , PAX6 , and NESTIN ), whilst also expressing a range of more specific genes (such as HOPX ). In primate brains, bRGs can divide multiple times, self-renewing and/or generating intermediate progenitors and neurons. They display a highly specific cytokinesis behavior termed mitotic somal translocation. We focus here on recently identified molecular mechanisms associated with the generation and amplification of bRGs, including bRG-like cells in the rodent. These include signaling pathways such as the FGF-MAPK cascade, SHH, PTEN/AKT, PDGF pathways, and proteins such as INSM, GPSM2, ASPM, TRNP1, ARHGAP11B, PAX6, and HIF1α. A number of these proteins were identified through transcriptome comparisons in human aRGs vs. bRGs, and validated by modifying their activities or expression levels in the mouse. This latter experiment often revealed enhanced bRG-like cell production, even in some cases generating folds (gyri) on the surface of the mouse cortex. We compare the features of the identified cells and methods used to characterize them in each model. These important data converge to indicate pathways essential for the production and expansion of bRGs, which may help us understand cortical development in health and disease.

show abstract

“…BAF155 mRNA is also regulated by methylation. In the developing mouse cortex, the m6A methyltransferase RBM15 interacts with BAF155 mRNA to regulate BAF155 expression levels, which in turn control the expression of adherens junction genes (Xie et al, 2019).…”

Section: Association With Nuclear Hormone Receptorsmentioning

confidence: 99%

Unwinding chromatin at the right places: how BAF is targeted to specific genomic locations during development

Lloyd

Bao

2019

Development

View full text Add to dashboard Cite

The BAF (SWI/SNF) chromatin remodeling complex plays a crucial role in modulating spatiotemporal gene expression during mammalian development. Although its remodeling activity was characterized in vitro decades ago, the complex actions of BAF in vivo have only recently begun to be unraveled. In living cells, BAF only binds to and remodels a subset of genomic locations. This selectivity of BAF genomic targeting is crucial for cell-type specification and for mediating precise responses to environmental signals. Here, we provide an overview of the distinct molecular mechanisms modulating BAF chromatin binding, including its combinatory assemblies, DNA/histone modification-binding modules and post-translational modifications, as well as its interactions with proteins, RNA and lipids. This Review aims to serve as a primer for future studies to decode the actions of BAF in developmental processes.

show abstract

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

Cited by 48 publications

References 59 publications

Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation

Chromatin remodelling factor BAF155 protects hepatitis B virus X protein (HBx) from ubiquitin-independent proteasomal degradation

Genes and Mechanisms Involved in the Generation and Amplification of Basal Radial Glial Cells

Unwinding chromatin at the right places: how BAF is targeted to specific genomic locations during development

Contact Info

Product

Resources

About