Fmrp Interacts with Adar and Regulates RNA Editing, Synaptic Density and Locomotor Activity in Zebrafish

• DOI: 10.1371/journal.pgen.1005702
• Publication Date: 2015-12-04T18:52:51Z
• Authors: Adi Shamay-Ramot; Khen Khermesh; Hagit T. Porath; Michal Barak; Yishay Pinto; Chaim Wachtel; Alona Zilberberg; Tali Lerer-Goldsh...; Sol Efroni; Erez Y. Levanon; Lior Appelbaum
• Keywords: ADAR; FMR1; RNA Silencing; Fragile X Syndrome

Fragile X syndrome (FXS) is the most frequent inherited form of mental retardation. The cause for this X-linked disorder silencing fragile retardation 1 (fmr1) gene and absence protein (Fmrp). RNA-binding Fmrp represses translation, particularly in synapses. In Drosophila, interacts with adenosine deaminase acting on RNA (Adar) enzymes. Adar enzymes convert to inosine (A-to-I) modify sequence transcripts. Utilizing fmr1 zebrafish mutant (fmr1-/-), we studied Fmrp-dependent neuronal circuit formation, behavior, Adar-mediated editing. By combining behavior analyses live imaging single axons synapses, showed hyperlocomotor activity, as well increased axonal branching synaptic density, fmr1-/- larvae. We identified thousands clustered editing sites transcriptome that biochemically Adar2a protein. expression levels adar genes Adar2 zebrafish. Microfluidic-based multiplex PCR coupled deep sequencing a mild increase A-to-I evolutionarily conserved Adar-targets These findings suggest loss results activity target-specific RNAs, which, turn, might alter formation FXS.