The Conserved, Disease-Associated RNA Binding Protein dNab2 Interacts with the Fragile X Protein Ortholog in Drosophila Neurons

Publication date: 8 August 2017
Source:Cell Reports, Volume 20, Issue 6
Author(s): Rick S. Bienkowski, Ayan Banerjee, J. Christopher Rounds, Jennifer Rha, Omotola F. Omotade, Christina Gross, Kevin J. Morris, Sara W. Leung, ChangHui Pak, Stephanie K. Jones, Michael R. Santoro, Stephen T. Warren, James Q. Zheng, Gary J. Bassell, Anita H. Corbett, Kenneth H. Moberg
The Drosophila dNab2 protein is an ortholog of human ZC3H14, a poly(A) RNA binding protein required for intellectual function. dNab2 supports memory and axon projection, but its molecular role in neurons is undefined. Here, we present a network of interactions that links dNab2 to cytoplasmic control of neuronal mRNAs in conjunction with the fragile X protein ortholog dFMRP. dNab2 and dfmr1 interact genetically in control of neurodevelopment and olfactory memory, and their encoded proteins co-localize in puncta within neuronal processes. dNab2 regulates CaMKII, but not futsch, implying a selective role in control of dFMRP-bound transcripts. Reciprocally, dFMRP and vertebrate FMRP restrict mRNA poly(A) tail length, similar to dNab2/ZC3H14. Parallel studies of murine hippocampal neurons indicate that ZC3H14 is also a cytoplasmic regulator of neuronal mRNAs. Altogether, these findings suggest that dNab2 represses expression of a subset of dFMRP-target mRNAs, which could underlie brain-specific defects in patients lacking ZC3H14.

Graphical abstract

Teaser

Drosophila dNab2 is an ortholog of an RNA binding protein lost in an inherited intellectual disability, but its neuronal role is undefined. Bienkowski et al. present evidence that dNab2 interacts with the fly fragile X ortholog (dFMRP), a key regulator of neuronal mRNA translation, and co-regulates neurodevelopment and function with dFMRP.


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