Characterization of unr; a gene closely linked to N-ras

The mammalian N-ras gene is believed to play a role in cellular proliferation, differentiation, and transformation. While investigating N-ras, we isolated cDNA's that originate from a closely linked upstream gene. RNase protection assays reveal that this gene, unr, is transcribed in the same direction as N-ras and that its 3' end is located just 130 base pairs away from the point at which N-ras transcription begins. The close spatial relationship between the two genes is conserved in all species from which the N-ras gene has been isolated. An open reading frame, potentially encoding a 798 amino acid protein, is contained within the unr cDNA. Neither the primary protein structure nor the nucleic acid sequence of unr is homologous to any other known gene, including N-ras. Unr transcripts are detected in mouse, rat and human cells, and Southern analysis indicates that the unr locus found immediately upstream of the N-ras gene is transcriptionaly active in the mouse since only a single copy of unr is detected in this species. Unr produces multiple transcripts that differ in their 3' ends and are apparently created through the differential use of multiple polyadenylation sites located in the 3' untranslated region of the gene. Both unr and N-ras are expressed in all tissues examined. In the testis, both genes are developmentally regulated, with an increase in expression occurring upon testicular maturation. Thus the two genes may be coordinately regulated, at least in certain circumstances. Our findings suggest that a thorough analysis of the relationship that exists between the two genes could potentially provide insights into the regulation and/or function of N-ras.