Poster abstracts
Poster number 45 submitted by Ullas Valiya Chembazhi
Function and regulation of alternative splicing to enhance tumor suppressor activity of Neurofibromin 2
Ullas V. Chembazhi (Department of Biochemistry, University of Illinois at Urbana-Champaign), Cole Lewis (Department of Biochemistry, University of Illinois at Urbana-Champaign), Miranda Gurra (Department of Biochemistry, University of Illinois at Urbana-Champaign), Auinash Kalsotra (Department of Biochemistry, University of Illinois at Urbana-Champaign)
Abstract:
Hippo signaling pathway functions as a central regulator of organ size in higher organisms, controlling cell proliferation and apoptosis. Recent studies in drosophila and mammals have shown that Neurofibromin 2 (NF2), a bona fide tumor suppressor, causes hippo pathway activation through direct binding and recruitment of LATS to the plasma membrane, promoting LATS phosphorylation by MST1/2-WW45. Nf2 encodes for two major isoforms that differ in the inclusion of exon-16 (E16) and possess distinct capacities to assume the active ‘open’ conformation. Here, we show that a conserved splicing switch in the Nf2 pre-mRNA occurs during postnatal mouse liver development, a period of extensive remodeling during which hepatocytes switch from a proliferative to quiescent state. A steady increase in the inclusion of E16, produces a structural change in the NF2 protein that causes it to act as a constitutive activator of hippo pathway. Further, using real-time and single-cell resolution biochromatic splicing reporter that monitors the exon 16 inclusion, we show that RBFOX2 (RNA Binding Fox-1 Homolog 2) directly regulates E16 splicing and that it is necessary to produce the adult isoform.
Keywords: Tumor suppressor, Rbfox2, developmentally regulated splicing