Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 23, Issue 12, Pages 4083-4093Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.23.12.4083-4093.2003
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Funding
- NCI NIH HHS [T32 CA062948, T32CA62948] Funding Source: Medline
- NIDA NIH HHS [DA07274, T32 DA007274] Funding Source: Medline
- NINDS NIH HHS [R01NS34151] Funding Source: Medline
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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.
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