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Far Upstream Element-Binding Protein 1 Regulates LSD1 Alternative Splicing to Promote Terminal Differentiation of
Inah Hwang1, Dongqing Cao2, Yoonmi Na1
1Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Stem Cell Reports
|April 3, 2018
Summary
Far upstream element-binding protein 1 (FUBP1) downregulation impairs neural cell differentiation and promotes brain tumors. Restoring FUBP1
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- Tumorigenesis involves genetic events disrupting terminal cell differentiation.
- Recurrent mutations in Far upstream element-binding protein 1 (FUBP1) are observed in low-grade gliomas.
- The role of FUBP1 in normal neurogenesis and its contribution to brain tumors remain unclear.
Purpose of the Study:
- To investigate the role of FUBP1 in neuronal differentiation and its involvement in tumorigenesis.
- To elucidate the molecular mechanisms by which FUBP1 influences neural development and tumor suppression.
Main Methods:
- Analysis of FUBP1 expression dynamics during neurogenesis.
- Investigating the impact of FUBP1 downregulation on neural progenitor differentiation.
- Assessing the collaborative effect of FUBP1 and IDH1R132H in tumorigenesis.
- Studying the splicing mechanism involving SRRM4, FUBP1, and the LSD1+8a isoform.
- Evaluating the rescue effect of LSD1+8a restoration in FUBP1-deficient cells.
Main Results:
- FUBP1 expression is dynamically regulated during neurogenesis, with downregulation impairing terminal differentiation.
- Loss of FUBP1 in neural progenitors promotes tumorigenesis, particularly in conjunction with IDH1R132H.
- FUBP1, through SRRM4, controls the splicing of the neurospecific LSD1+8a isoform, crucial for neuronal maturation.
- Downregulation of LSD1+8a upon FUBP1 loss impairs neuronal differentiation and maturation.
- Restoring LSD1+8a expression rescues differentiation and suppresses tumorigenesis in FUBP1-deficient cells.
Conclusions:
- FUBP1 plays a critical role in regulating neuronal differentiation and maturation.
- LSD1+8a is an essential downstream effector of FUBP1-mediated neuronal differentiation.
- FUBP1 functions as a tumor suppressor in the nervous system by maintaining neuronal differentiation.
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