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Author Notes:

Correspondence: acorbe2@emory.edu (A.H.C.) and kmoberg@emory.edu

Conceptualization, R.S.B., K.H.M. and A.H.C; Methodology, R.S.B., K.H.M., and A.H.C.; Investigation, R.S.B., A.B., J.C.R, J.O., J.R., S.L., C.G., C.P., K.J.M., S.K.J., and M.R.S.; Writing-Original Draft, R.S.B. and K.H.M.; Writing-Review and Editing, R.S.B., K.H.M., and A.H.C.; Resources, S.T.W., G.J.B. and J.Q.Z.; Supervision, K.H.M., A.H.C., S.T.W., G.J.B. and J.Q.Z.; Funding Acquisition, K.H.M., A.H.C., and R.S.B.

We thank Bloomington Drosophila Stock Center (Indiana) and Developmental Studies Hybridoma Bank (Iowa) for stocks and antibodies.

We are grateful to S. Kelly for assistance with brain dissection and neuronal culture, and to T. Jongens, S. Kunes, M. Metzstein, M. Simonelig and D. Bilder for providing stocks, and S. Sanyal for the T-mazes.

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Research Funding:

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:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • MENTAL-RETARDATION PROTEIN
  • MESSENGER-RNA
  • TRANSLATIONAL CONTROL
  • POLYADENOSINE RNA
  • DEPENDENT TRANSLATION
  • MEMORY FORMATION
  • CAMKII FUNCTION
  • FMRP
  • PATHWAY
  • SYNAPSES

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

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Journal Title:

Cell Reports

Volume:

Volume 20, Number 6

Publisher:

, Pages 1372-1384

Type of Work:

Article | Final Publisher PDF

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.

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© 2017 The Author(s)

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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