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

• Type of Material: Article
• Authors: Rick S. Bienkowski, Emory University; Ayan Banerjee, Emory University; J. Christopher Rounds, Emory University; Jennifer Rha, Emory University; Omotola F. Omotade, Emory University; Christina Gross, University of Cincinnati; Kevin J. Morris, Emory University; Sara Leung, Emory University; ChangHui Pak, Emory University; Stephanie K. Jones, Emory University; Michael R. Santoro, Emory University; Stephen Warren, Emory University; James Zheng, Emory University; Gary Bassell, Emory University; Anita Corbett, Emory University; Kenneth Moberg, Emory University
• Language: English
• Date: 2017-08-08
• Publisher: Elsevier (Cell Press): OAJ
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Author(s)
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2017.07.038
• Title of Journal or Parent Work: Cell Reports
• ISSN: 2211-1247
• Volume: 20
• Issue: 6
• Start Page: 1372
• End Page: 1384
• Grant/Funding Information: Financial support: MH10730501 (K.H.M. and A.H.C.), MH109026 (G.J.B.), U54-NS091859 (S.T.W.), GM083889, MH104632, and MH108025 (J.Q.Z), F31-NS092437 (O.F.O) and F31-HD07922601 (R.S.B.).
• Keywords: MESSENGER-RNA; MENTAL-RETARDATION PROTEIN; DEPENDENT TRANSLATION; SYNAPSES; MEMORY FORMATION; TRANSLATIONAL CONTROL; POLYADENOSINE RNA; Science & Technology; CAMKII FUNCTION; Cell Biology; FMRP; PATHWAY; Life Sciences & Biomedicine
• Research Categories: Biology, Genetics; Biology, General; Chemistry, Biochemistry

Abstract

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.