NABP1, a novel RORγ-regulated gene encoding a single-stranded nucleic-acid-binding protein

ROR gamma 2 (retinoid-related orphan receptor gamma 2) plays a critical role in the regulation of thymopoiesis. Microarray analysis was performed in order to uncover differences in gene expression between thymocytes of wild-type and ROR gamma(-/-) mice. This analysis identified a novel gene encoding a 22kDa protein, referred to as NABP1 (nucleic-acid-binding protein 1). This subsequently led to the identification of an additional protein, closely related to NABP1, designated NABP2. Both proteins contain and OB (oligonucleotide/oligosaccharide binding) motif at their N-terminus. This motif is highly conserved between the two proteins. NABP1 is highly expressed in the thymus of wild-type mice and is greatly suppressed in ROR gamma(-/-) mice. During thymopoiesis, NABP1 mRNA expression is restricted to CD4(+)CD8(+) thymocytes, an expression pattern similar to that observed for ROR gamma 2. These observations appear to suggest that NABP1 expression is regulated either directly or indirectly by ROR gamma 2. Confocal microscopic analysis showed that the NABP1 protein localizes to the nucleus. Analysis of nuclear proteins by size-exclusion chromatography indicated that NABP I is part of a high molecular-mass protein complex. Since the OB-fold is frequently involved in the recognition of nucleic acids, the interaction of NABP1 with various nucleic acids was examined. Our results demonstrate that NABP1 binds single-stranded nucleic acids, but not double-stranded DNA, suggesting that it functions as a single-stranded nucleic acid binding protein.