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Dissecting the Molecular Determinants that Mediate Protein/RNA Interactions at the Synapse
Author(s) -
Mirkovic Jovan,
Hossain Md. Faruk,
Stolfi Alberto,
Wang Ruizhi,
Stitzel Henry,
Christiaen Lionel,
Ruggiu Matteo
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.790.3
Subject(s) - agrin , biology , alternative splicing , neuromuscular junction , synapse , acetylcholine receptor , rna splicing , microbiology and biotechnology , rna , exon , gene , genetics , neuroscience , receptor
The NOVA family of RNA‐binding proteins consists of neuron‐specific splicing regulators that are targeted in an autoimmune neurodegenerative motor disorder. They are sequence‐specific splicing factors, with a modular structure consisting of three KH domains that mediate protein‐RNA interactions. One of the targets of NOVA is a neuron‐specific isoform of the ubiquitously expressed gene AGRIN. This splice variant, termed Z + AGRIN, is secreted by neurons and is found at the synaptic cleft at the neuromuscular junction (NMJ), a synapse between a nerve cell and a muscle cell, and the best‐studied model synapse. By inducing the clustering of acetylcholine receptors (AChR) on the postsynaptic membrane, Z + AGRIN promotes the formation, maintenance, and development of the NMJ. The Z exons are also of particular interest as they are potential mutation sites in congenital neuromuscular diseases. The study of NOVA function in vertebrates is complicated by the presence of two NOVA genes termed NOVA1 and NOVA2. The tunicate Ciona robusta is a marine invertebrate that is the closest living relative to vertebrates. Interestingly, Ciona has only one Nova gene. We used the NOVA‐AGRIN paradigm to study the evolution of nerve cell specific protein‐RNA interactions. We cloned and characterized Nova proteins from Ciona and generated Agrin minigenes that recapitulate the action of Nova in a tissue culture cell system. Here, we identify the specific Agrin pre‐mRNA nucleotide sequences that mediate Nova‐dependent splicing of Z + agrin in tunicates. Support or Funding Information National Institutes of Health This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .