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

ROR β is a member of the nuclear hormone receptor superfamily whose ligand is unknown. Expression of ROR β 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 β 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 β from rat pineal tissue. Expression of this isoform, called ROR β2, is confined to pineal gland and retina and strongly increases at night. ROR β2 shares common DNA- and putative ligand-binding domains with the canonical ROR β (referred to as ROR β1), but is characterized by a different amino-terminal domain. This structural difference renders ROR β2 much more selectively binding to DNA than ROR β1. Moreover, in contrast to ROR β1, the novel isoform efficiently activates transcription also in non-neuronal cell lines. Thus, the two ROR β isoforms are likely to regulate different sets of genes in different physiological contexts.