A NOVEL ISOFORM OF THE ORPHAN NUCLEAR RECEPTOR ROR-BETA 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 recep tor is implicated in the processing of sensory information and in circ adian timing. In rats, ROR beta mRNA levels oscillate robustly in pine al gland and retina, displaying a 24 h rhythm. Here we report the clon ing 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 co mmon DNA- and putative ligand-binding domains with the canonical ROR b eta (referred to as ROR beta 1), but is characterized by a different a mino-terminal domain. This structural difference renders ROR beta 2 mu ch more selectively binding to DNA than ROR beta 1. Moreover, in contr ast to ROR beta 1, the novel isoform efficiently activates transcripti on also in non-neuronal cell lines. Thus, the two ROR beta isoforms ar e likely to regulate different sets of genes in different physiologica l contexts. (C) 1998 Elsevier Science B.V. All rights reserved.