Liu Wencheng, Seto Jeremy, Sibille Etienne, Toth Miklos
Department of Pharmacology, Weill Medical College of Cornell University. Graduate Program in Neuroscience, Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10021, USA.
Mol Cell Biol. 2003 Jun;23(12):4083-93. doi: 10.1128/MCB.23.12.4083-4093.2003.
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.
小鼠中Jerky蛋白的缺陷会导致反复发作的癫痫，类似于颞叶癫痫。Jerky存在于神经元的mRNA颗粒中。我们发现，Jerky的N端168个氨基酸对于mRNA结合是必要且充分的。该结合结构域类似于着丝粒结合蛋白B的两个串联排列的类同源结构域螺旋-转角-螺旋DNA结合基序。Jerky的推定螺旋-转角-螺旋基序也能结合双链DNA，并代表一种新型的哺乳动物RNA/DNA结合结构域。微阵列分析确定了编码参与核糖体组装和细胞应激反应的蛋白质的mRNA，这些mRNA在体外和体内均能特异性结合Jerky的RNA结合结构域。这些数据表明，Jerky缺陷小鼠的癫痫发生很可能涉及与核糖体生物发生以及神经元存活和/或凋亡相关的途径。
