Ph.D. National Tsing Hua University
Postdoc Assoc. Yale University
Post-transcriptional regulation in neuronal and cancer cells
My laboratory focuses on mRNA splicing and translation control in neuron and cancer, as well as the cellular function of lncRNAs. Alternative splicing provides a means for development- and tissue-specific gene expression. We investigate how alternative splicing programs neuronal cell differentiation and impacts brain development. The RNA binding protein RBM4 plays a role in neuronal cell differentiation and radial glial migration via alternative splicing regulation. Rbm4 knockout impaired neurotrophic signaling and hence affected cerebellar foliation. Prenatal supplementation of neurotrophin receptor agonist can rescue cerebellar development of newborn mice (submitted). RBM4 indeed regulates alternative splicing of the upstream regulators of neurotrophic signaling. In our second project, we study how RNA helicase DDX3-mediated translational control influences cancer progression. We recently reported that DDX3 promotes the translation of secretory oncogenic factors via its association with the signal recognition particle on the ER. Cancer-derived mutants of DDX3 exert higher potential to translate those pro-tumorigenic factors and hence contribute to the pro-tumorigenic microenvironment. More recently, we found that DDX3 regulates tumor immune surveillance. Therefore, inhibition of DDX3 may be an adjuvant therapy for anti-cancer treatment. In our third project, we study the role of an lncRNA in DNA double strand break (DSB) repair. We identified an lncRNA ribonucleoprotein complex containing both RNA processing and DNA repair factors. This lncRNA recruits specific ribonucleases to degrade DSB induced transcripts at DNA lesions (revised). Finally, we found that this lncRNA can co-phase separate with a RNA processing factor to form liquid-like droplets, suggesting DNA repair condensates at damage sites (revised). We would continue to unveil the importance of RNA regulation.