CNBP, the product of ZNF9 gene mutated in Myotonic Dystrophy Type 2, is a nucleic acid chaperone that favours G-quadruplex formation and controls cell proliferation in neural crest development.

ARMAS, P.; WEINER, A. M. J.; BORGOGNONE, M.; CALCATERRA, N. B.

Washington, DC

Conferencia; 6th Brain Research Meeting: RNA Proteins in Neurological Disease.; 2011

Elsevier Ltd.

Cellular nucleic acid binding protein (CNBP) is encoded by the ZNF9 gene. In humans, anexpansion of CCTG repeats in intron 1 of ZNF9 gene causes Myotonic Dystrophy type 2 (DM2).DM2 may be caused by: (i) disruption of RNA by accumulation of untranslated CCUGn RNAsand (ii) reduction of the global protein synthesis due to reduced CNBP levels. CNBP was alsoimplicated in craniofacial development and sporadic inclusion body myositis (sIBM) humandisease.CNBP is a small and highly conserved single-stranded nucleic acid binding protein able to bindsingle stranded DNA and RNA. CNBP has a broad spectrum of targets, ranging from DNAregulatory sites in gene promoters to RNA translational regulatory elements in untranslatedregions of mRNAs. CNBP binds G-rich single-stranded nucleic acids and acts as a nucleic acidchaperone and favours the folding in vitro of parallel intramolecular G-quadruplex structures.Moreover, CNBP activates the c-myc proto-oncogene transcription in cell cultures though astable G-quadruplex forming sequence present in the human c-myc promoter.CNBP depletion causes defects in the pharyngeal skeleton derived from the neural crest (NC)cells, as demonstrated by reduced expression of typical NC marker genes and col2a1, aspecific marker gene for craniofacial cartilage. Higher apoptosis and lower cell proliferation inthe anterior-most region of CNBP-depleted embryos were also detected. Therefore, CNBPdepletion may lead to a deficit of NC cells and, consequently, neurocranial truncation,disorganization, and disruption of pharyngeal cartilages.Collectively, CNBP appears to be involved in controlling cell death and proliferation rates. Lowlevels of CNBP may reduce rate of global protein synthesis, thereby reducing proliferation andincreasing apoptosis. Conversely, CNBP might affect transcription of genes required for cellproliferation. Experimental evidences gathered so far make it difficult to ascertain or rule out anyof these possibilities, which may not be mutually exclusive.