BBA - Gene Regulatory Mechanisms
Regulation of gene function in the brain
Edited by S. Ryder and N.R. Zearfoss
Volume 1779, Issue 8 (August 2008)

The brain is composed of multiple highly differentiated and polarized cell types that form a precisely connected network. Communications between the cells, which are often restricted to specific subcellular regions, form the molecular basis of neural function. The intricacy of the cellular network in the brain requires precise control of gene expression at every stage, as information flows from genes to RNA to protein. In this collection of reviews, we highlight the diversity of the mechanisms by which cells control expression of their genes in the brain. The reviews are organized to roughly follow the flow of information in a cell.

The first two reviews deal with gene expression at the level of transcription. The first, by Weeber and colleagues, describes the regulation of Reelin, a brain protein that triggers a signaling cascade that has been implicated in several human diseases. The second review, by Yi Sun and co-workers, takes a broad look at epigenetic mechanisms that influence gene expression during neural differentiation. Following these reviews is a group of reviews that highlight different post-transcriptional mechanisms by which the brain regulates gene expression. In the first, Jiuyong Xie reviews the growing evidence that calcium signaling controls alternative splicing in neural cells. The next review, by Barbarese and colleagues, describes the mechanism of subcellular mRNA localization in the brain, a process that allows RNAs to be utilized more rapidly and efficiency than if they were found cell-wide. Following are reviews by Jepson and Reenan, who describe the evidence supporting RNA editing in neurons and its role in controlling synaptic transmission in the brain, and Schratt and colleagues, who describe the microRNAs that have been identified in the brain and their role in regulating brain function. The next two RNA-centered reviews focus on RNA binding proteins: the first, by Baraban and co-workers, describes the translin:trax RNA binding complex, and the second, by Ryder and colleagues, describes the RNA binding proteins expressed in the oligodendrocyte lineage, including Quaking, and their effects on myelination. The final two reviews describe post-translational mechanisms of gene expression regulation, first at the level of protein stability in a review by Haas and Broadie specifically dealing with ubiquitination at the synapse, and second at the level of protein function, in a review by Wyttenbach and co-workers, who discuss the function of polyglutamine genes as related to aging.

By highlighting the diversity of mechanisms that control gene expression during brain development and in the mature brain, we hope to emphasize to readers that in this highly complex tissue, nothing can be taken for granted, and that for any given gene, expression is almost certainly controlled at multiple levels. We hope the following reviews spur the imagination and inspire creativity as readers seek to understand the molecular mechanisms that underlie the function of the brain.