Abstract
A deficit in the Jerky protein in mice causes recurrent seizures reminiscent of temporal lobe epilepsy. Jerky is present in mRNA particles in neurons. We show that the N-terminal 168 amino acids of Jerky are necessary and sufficient for mRNA binding. The binding domain is similar to the two tandemly arranged homeodomain-like helix-turn-helix DNA binding motifs of centromere binding protein B. The putative helix-turn-helix motifs of Jerky can also bind double-stranded DNA and represent a novel mammalian RNA/DNA binding domain. Microarray analysis identified mRNAs encoding proteins involved in ribosome assembly and cellular stress response that specifically bound to the RNA binding domain of Jerky both in vitro and in vivo. These data suggest that epileptogenesis in Jerky-deficient mice most likely involves pathways associated with ribosome biogenesis and neuronal survival and/or apoptosis.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Apoptosis
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Cell Line
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DNA / metabolism
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DNA, Complementary / metabolism
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Epilepsy / genetics
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Epilepsy / pathology
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Glutathione Transferase / metabolism
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Humans
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Kinetics
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Mice
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Molecular Sequence Data
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Mutation
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / genetics*
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Neurons / metabolism
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Oligonucleotide Array Sequence Analysis
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Protein Binding
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Protein Structure, Tertiary
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RNA / metabolism*
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RNA, Messenger / metabolism
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RNA-Binding Proteins
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Transfection
Substances
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DNA, Complementary
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DNA-Binding Proteins
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Nerve Tissue Proteins
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RNA, Messenger
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RNA-Binding Proteins
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jrk protein, mouse
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RNA
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DNA
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Glutathione Transferase