Originally published as Genetics Published Articles Ahead of Print on December 28, 2006.

Genetics, Vol. 175, 1241-1250, March 2007, Copyright © 2007
doi:10.1534/genetics.106.068908

Substitution of Critical Isoleucines in the KH Domains of Drosophila Fragile X Protein Results in Partial Loss-of-Function Phenotypes

Paromita Banerjee^*, Shweta Nayar^*, Sarita Hebbar^*,1, Catherine F. Fox^*,2, Michele C. Jacobs^*,3, Jae H. Park, Joyce J. Fernandes^* and Thomas C. Dockendorff^*,4

^* Department of Zoology, Miami University, Oxford, Ohio 45056 and Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee 37996

⁴ Corresponding author: Department of Zoology, Miami University, 212 Pearson Hall, 700 E. High St., Oxford, OH 45056.
E-mail: dockentc{at}muohio.edu

Fragile X mental retardation proteins (FMRP) are RNA-binding proteins that interact with a subset of cellular RNAs. Several RNA-binding domains have been identified in FMRP, but the contribution of these individual domains to FMRP function in an animal model is not well understood. In this study, we have generated flies with point mutations in the KH domains of the Drosophila melanogaster fragile X gene (dfmr1) in the context of a genomic rescue fragment. The substitutions of conserved isoleucine residues within the KH domains with asparagine are thought to impair binding of RNA substrates and perhaps the ability of FMRP to assemble into mRNP complexes. The mutants were analyzed for defects in development and behavior that are associated with deletion null alleles of dfmr1. We find that these KH domain mutations result in partial loss of function or no significant loss of function for the phenotypes assayed. The phenotypes resulting from these KH domain mutants imply that the capacities of the mutant proteins to bind RNA and form functional mRNP complexes are not wholly disrupted and are consistent with biochemical models suggesting that RNA-binding domains of FMRP can function independently.

This article has been cited by other articles:

				S. P. Reeve, X. Lin, B. H. Sahin, F. Jiang, A. Yao, Z. Liu, H. Zhi, K. Broadie, W. Li, A. Giangrande, et al. Mutational Analysis Establishes a Critical Role for the N Terminus of Fragile X Mental Retardation Protein FMRP J. Neurosci., March 19, 2008; 28(12): 3221 - 3226. [Abstract] [Full Text] [PDF]

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