Expression in the human brain of retinoic acid induced 1, a protein associated with neurobehavioural disorders

Abstract

Retinoic acid induced 1 (RAI1) is a protein of uncertain mechanism of action which nevertheless has been the focus of attention because it is a major contributing factor in several human developmental disorders including Smith–Magenis and Potocki–Lupski syndromes. Further, RAI1 may be linked to adult neural disorders with developmental origins such as schizophrenia and autism. The protein has been extensively examined in the rodent but very little is known about its distribution in the human central nervous system. This study demonstrated the presence of RAI1 transcript in multiple regions of the human brain. The cellular expression of RAI1 protein in the human brain was found to be similar to that described in the mouse, with high levels in neurons, but not glia, of the dentate gyrus and cornus ammonis of the hippocampus. In the cerebellum, a second region of high expression, RAI1 was present in Purkinje cells, but not granule cells. RAI1 was also found in neurons of the occipital cortex. The expression of this retinoic acid-induced protein matched well in the hippocampus with expression of the retinoic acid receptors. The subcellular distribution of human neuronal RAI1 indicated its presence in both cytoplasm and nucleus. Overall, human RAI1 protein was found to be a highly expressed neuronal protein whose distribution matches well with its role in cognitive and motor skills.

Rai1 frees mice from the repression of active wake behaviors by light

“…Rai1 is widely expressed throughout the brain with high levels of expression observed in the olfactory bulb, cerebral cortex, hippocampus, striatum, thalamus, hypothalamus, cerebellum, and brainstem (Toulouse et al, 2003; Bi et al, 2007; Fragoso et al, 2015; Huang et al, 2016). Because circadian and/or light-dependent changes in Rai1 expression in the brain may contribute to the phenotypes we observed in Rai1 -haploinsufficient mice, we sampled brain tissue under LD12:12 conditions at 3-hr intervals in wild-type mice.…”

“…RAI1 is a highly conserved transcriptional regulator (Carmona-Mora et al, 2010) with high neuronal expression (Toulouse et al, 2003; Fragoso et al, 2015), and recent evidence shows that it acts as a positive transcriptional regulator by binding to active promotor and enhancer regions (Huang et al, 2016). Among RAI1 target genes are Bdnf ( brain-derived neurotrophic factor ) and Htr2c ( serotonin receptor 2c ) (Huang et al, 2016; Burns et al, 2010), both of which are implicated in hyperphagia leading to obesity, a phenotype accompanying SMS, concomitant with altered locomotor activity (Huang et al, 2016; Burns et al, 2010; Kernie et al, 2000; Nonogaki et al, 2003).…”

Identification of Potocki–Lupski syndrome in patients with developmental delay and growth failure

“…Here we describe the three Korean patients with PTLS due to a duplication of 17p11. 2 The clinical features of our patient will help to understand this rare genetic condition.…”

“…The RAI1 gene was first isolated in 1995 [10]. RAI1 is expressed in human hippocampus, cortex and cerebellum, and is suggested to be associated with cognitive and motor nervous function [2]. RAI1 is a transcription factor but its precise mode of action is unclear.…”

“…The region includes retinoic acid-induced protein 1 (RAI1) gene. Although the role of this gene is elusive, it has been suggested as associated with the psychiatric disorders such as developmental delay, schizophrenia and autism [2].…”