Abstract
BackgroundIn eukaryotic cells, RNA-binding proteins (RBPs) contribute to gene expression by regulating the form, abundance, and stability of both coding and non-coding RNA. In the vertebrate brain, RBPs account for many distinctive features of RNA processing such as activity-dependent transcript localization and localized protein synthesis. Several RBPs with activities that are important for the proper function of adult brain have been identified, but how many RBPs exist and where these genes are expressed in the developing brain is uncharacterized.ResultsHere we describe a comprehensive catalogue of the unique RBPs encoded in the mouse genome and provide an online database of RBP expression in developing brain. We identified 380 putative RBPs in the mouse genome. Using in situ hybridization, we visualized the expression of 323 of these RBP genes in the brains of developing mice at embryonic day 13.5, when critical fate choice decisions are made and at P0, when major structural components of the adult brain are apparent. We demonstrate i) that 16 of the 323 RBPs examined show neural-specific expression at the stages we examined, and ii) that a far larger subset (221) shows regionally restricted expression in the brain. Of the regionally restricted RBPs, we describe one group that is preferentially expressed in the E13.5 ventricular areas and a second group that shows spatially restricted expression in post-mitotic regions of the embryonic brain. Additionally, we find a subset of RBPs that share the same complex pattern of expression, in proliferating regions of the embryonic and postnatal NS and peripheral tissues.ConclusionOur data show that, in contrast to their proposed ubiquitous involvement in gene regulation, most RBPs are not uniformly expressed. Here we demonstrate the region-specific expression of RBPs in proliferating vs. post-mitotic brain regions as well as cell-type-specific RBP expression. We identify uncharacterized RBPs that exhibit neural-specific expression as well as novel RBPs that show expression in non-neural tissues. The data presented here and in an online database provide a visual filter for the functional analysis of individual RBPs.
Highlights
In eukaryotic cells, RNA-binding proteins (RBPs) contribute to gene expression by regulating the form, abundance, and stability of both coding and non-coding RNA
The ordered production and differentiation of cell types that occurs during nervous system (NS) development relies upon tightly regulated gene expression
Mouse RBPs were identified according to gene sequence The RNA recognition motif (RRM), the hnRNP K-homology (KH) domain, and the double-stranded RNA-binding domain are evolutionarily conserved, well-characterized domains known to bind either single or doublestranded RNA [27,28,29]
Summary
RNA-binding proteins (RBPs) contribute to gene expression by regulating the form, abundance, and stability of both coding and non-coding RNA. RBPs account for many distinctive features of RNA processing such as activity-dependent transcript localization and localized protein synthesis. The ordered production and differentiation of cell types that occurs during nervous system (NS) development relies upon tightly regulated gene expression. Spatial and temporal gene regulation occurs through both transcriptional and post-transcriptional mechanisms. While the transcriptional networks that direct neural cell fate and govern cell shape, position, and connectivity have been well studied [1,2,3], the post-transcriptional influences on neural development and gene expression are less well understood. At the core of post-transcriptional gene regulation are RNA-binding proteins (RBPs). Specific RBPs enable asymmetric RNA distribution and translational regulation [8,9,10], two phenomena that are critical for affecting localized protein synthesis [11,12]
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