Full UPF3B function is critical for neuronal differentiation of neural stem cells

3^rd International Conference on Genomics & Pharmacogenomics

September 21-23, 2015 San Antonio, USA

Tahani Mohammed Ameen Alrahbeni1,2

1Riyadh Colleges of Dentistry and Pharmacy, Saudi Arabia 2University of Aberdeen, UK

Posters-Accepted Abstracts: J Mol Genet Med

Abstract :

Mutation in the UPF3B gene on chromosome X is implicated in neuro-developmental disorders including X-linked intellectual disability, autism and schizophrenia. The protein UPF3B is involved in the Nonsense-Mediated mRNA Decay pathway (NMD) that controls mRNA stability and functions in the prevention of the synthesis of truncated proteins. Here, we show that NMD pathway components UPF3B and UPF1 are down regulated during differentiation of neural stem cells into neurons. Using tethered function assays we found that UPF3B missense mutations described in families with neuro-developmental disorders reduced the activity of UPF3B protein in NMD. In neural stem cells, UPF3B was detected in the cytoplasm and in the nucleus where it was enriched in the nucleolus. A similar distribution was observed in neurons. Using GFP tagged UPF3B proteins; we found that the missense mutations did not affect cellular localisation. Expression of missense mutant UPF3B disturbed neuronal differentiation and reduced the complexity of the branching of neurites. Neuronal differentiation was similarly affected in the presence of the NMD inhibitor Amlexanox. The expression of mutant UPF3B proteins lead to a subtle increase in mRNA levels of selected NMD targets. Together this indicates that despite the downregulation of NMD factors, functional NMD is critical for neuronal differentiation. We propose that the neuro-developmental phenotype of UPF3B missense mutation is caused by impairment of NMD function altering neuronal differentiation.

Biography :

Email: ph.tahani@riyadh.edu.sa