Modulation of a Novel RNA in Brain Neurons by Glucocorticoid and Mineralocorticoid Receptors

Abstract

A novel cDNA clone, CR16, was isolated from a rat hippocampal cDNA library and characterized for responses to corticosteroids and regional expression. The 4-kb RNA was increased 3-fold by treatment of adrenalectomized (ADX) rats with corticosterone (CORT). Overlapping cDNA totaling 4,374 nt were used to define an open reading frame of 1,356 nt beginning 191 nt from the 5’-end and encoding a 45-kD protein containing 32% proline. CR16 has no obvious homologies to GenBank or protein databases. CR16 RNA was detected by in situ hybridization in neuron-rich layers of the hippocampal formation, layers II, III and VI of the cerebral cortex, thalamus, ventromedial nucleus of the hypothalamus, bed nucleus of the stria terminalis, lateral septal nucleus, nucleus accumbens, olfactory bulb, inferior colliculus, pons and inferior olive. The CR16 RNA has low prevalence in the hippocampus and cortex (<10 pg/µg total RNA) and is elevated 3-fold in both structures in a dose-dependent manner by CORT in ADX rats. Treatment of ADX rats with aldosterone (ALDO), CORT, or RU28362 increased CR16 RNA to similar levels in the hippocampus while ALDO had minimal effects on the level of CR16 RNA relative to CORT or RU28362 in the cortex. Neither shaking stress (2 h) nor 2 h CORT significantly elevated CR16 RNA in the hippocampus, suggesting that its response to elevated CORT is not rapid. ADX lowered CR16 RNA levels by 50% relative to intact rats while low-level CORT replacement (≧4 ng/ml serum CORT) significantly elevated CR16 RNA 2-fold in ADX rats. These results are consistent with both the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) regulating the CR16 gene. This gene will be useful in dissecting the role of MR and GR in CNS neurons.

A Complex of Wiskott-Aldrich Syndrome Protein with Mammalian Verprolins Plays an Important Role in Monocyte Chemotaxis

“…CR16 was identified as a glucocorticoid-enhanced gene product and is expressed predominantly in the brain. CR16 and N-WASP colocalize and function in primary hippocampal neuron (26,33).…”

CR16 forms a complex with N-WASP in brain and is a novel member of a conserved proline-rich actin-binding protein family

“…2). CR16 was originally cloned as a glucocorticoid-regulated mRNA from a rat hippocampal cDNA library (14,15). The CR16 ORF predicts a 49-kDa protein with an unusually high proline content (32%), which likely contributes to its aberrant migration at 67 kDa on SDS͞PAGE and perhaps its reduced dye binding.…”

“…The CR16 mRNA was previously reported to be expressed in brain, heart, lung, and testis but not kidney, liver, and spleen (15). We sought to determine the tissue and subcellular distribution of CR16 protein.…”

The Genomic Response of Skeletal Muscle to Methylprednisolone Using Microarrays: Tailoring Data Mining to the Structure of the Pharmacogenomic Time Series

“…However, there are a large number of genes whose transcription is altered indirectly by glucocorticoids. In these cases, glucocorticoids alter the expression or function of other transcription factors, which in turn alter the transcription of other genes [13,[18][19][20][21][22]. Although still not entirely understood, the phenomena of muscle wasting and insulin resistance clearly involve temporal cascades of changes in the expression of a multiplicity of genes [2][3][4][5]19,[23][24][25][26].…”