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Molecular and Cellular Biology, June 2003, p. 4083-4093, Vol. 23, No. 12
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.12.4083-4093.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The RNA Binding Domain of Jerky Consists of Tandemly Arranged Helix-Turn-Helix/Homeodomain-Like Motifs and Binds Specific Sets of mRNAs

Wencheng Liu,1 Jeremy Seto,2 Etienne Sibille,3 and Miklos Toth1,2*

Department of Pharmacology, Weill Medical College of Cornell University,1 Graduate Program in Neuroscience, Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10021,2 Department of Neuroscience, NYS Psychiatric Institute at Columbia University, New York, New York 100323

Received 7 February 2003/ Returned for modification 5 March 2003/ Accepted 18 March 2003

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.

* Corresponding author. Mailing address: Department of Pharmacology, Weill Medical College of Cornell University, 1300 York Ave., LC 522, New York, NY 10021. Phone: (212) 746-6245. Fax: (212) 746-8835. E-mail: mtoth{at}mail.med.cornell.edu.

Molecular and Cellular Biology, June 2003, p. 4083-4093, Vol. 23, No. 12
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.12.4083-4093.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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