LncRNA Pnky Positively Regulates Neural Stem Cell Migration via Modulating mRNA Splicing and Export of Target Genes

Abstract

Directed migration of neural stem cells (NSCs) is critical for embryonic neurogenesis and the healing of neurological injuries. LncRNA Pnky was reported to regulate neuronal differentiation of NSCs. However, its regulatory effect on NSC migration has never been explored. Herein, we identified that Pnky was also a key regulator of NSC migration, as underscored by the fact that Pnky silencing restrained the migration of both NSC lines C17.2 and NE4C, whereas Pnky over-expression promoted their migration. Meanwhile, Pnky regulated the expression of a core set of critical regulators that directing NSC migration, such as MMP2, MMP9, AKT and p38MAPK, etc. Through preliminary bioinformatics, we surprisingly noticed that splicing factors U2AF1 and U2AF1L4, as well as mRNA export adaptors SARNP, Aly/Ref and THOC7, were predicted to strongly interact with Pnky. Mechanically, Pnky could co-localize and directly bind to U2AF1, SARNP, Aly/Ref and THOC7, indicating the involvement of Pnky in modulating mRNA splicing and export processes. Collectively, our data delineated that, through interacting with U2AF1, SARNP, Aly/Ref and THOC7, Pnky coupled and modulated the mRNA splicing and export of downstream factors, which consequently affected NSC migration. These findings provide a possible theoretical basis of NSC migration for brain development and damage repair.