A novel isoform of the orphan nuclear receptor RORβ is specifically expressed in pineal gland and retina

ROR beta is a member of the nuclear hormone receptor superfamily whose ligand is unknown. Expression of ROR beta is confined to the central nervous system and its pattern suggests that this orphan nuclear receptor is implicated in the processing of sensory information and in circadian timing. In rats, ROR beta mRNA levels oscillate robustly in pineal gland and retina, displaying a 24 h rhythm. Here we report the cloning of the cDNA of a novel isoform of ROR beta from rat pineal tissue. Expression of this isoform, called ROR beta 2, is confined to pineal gland and retina and strongly increases at night. ROR beta 2 shares common DNA- and putative ligand-binding domains with the canonical ROR beta (referred to as ROR beta 1), but is characterized by a different amino-terminal domain. This structural difference renders ROR beta 2 much more selectively binding to DNA than ROR beta 1. Moreover, in contrast to ROR beta 1, the novel isoform efficiently activates transcription also in non-neuronal cell lines. Thus, the two ROR beta isoforms are likely to regulate different sets of genes in different physiological contexts. (C) 1998 Elsevier Science B.V. All rights reserved.