Filamin A inhibits neural stem cell self-renew by downregulating rDNA transcription

Neural stem cells (NSCs) are the basis of neurogenesis and neural regeneration and are widely used as models for drug test and disease therapy. However, how NSCs self-renewal is modulated is not fully understood. In this study, we show that cytoskeletal Filamin A (FLNA) acts as a negative regulator in NSCs proliferation or self-renew. FLNA can be localized to the nucleoli of both NE-4C and C17.2 cell lines. FLNA silencing activated the expression of Pol Ⅰ products. In contrast, FLNA overexpression dampened rDNA transcription, suggesting that FLNA suppresses NSCs proliferation by downregulating Pol Ⅰ-directed transcription. Mechanistically, FLNA downregulates Pol I-directed transcription by inhibiting RRN3 expression and the occupancies of the Pol I transcription machinery factors at the rDNA promoter. In addition, FLNA suppresses NSCs proliferation by maintaining high levels of P53 and PTEN expression. Finally, we show that FLNA silencing does not affect the identity of neural stem cells, but inhibits neuronal differentiation from neural stem cells. These findings provide a novel insight into the mechanisms by which FLNA negatively regulates NSCs self-renew.